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[ { "id": "PMID-1419903__text", "type": "abstract", "text": [ "Regulation of c-jun expression during induction of monocytic differentiation by okadaic acid. \nThe present work has examined the effects of okadaic acid, an inhibitor of type 1 and 2A protein phosphatases, on the regulation of c-jun expression during monocytic differentiation of U-937 leukemia cells. The results demonstrate that okadaic acid treatment is associated with induction of a differentiated monocyte phenotype characterized by: (a) growth arrest; (b) increases in Mac-1 cell surface antigen expression; (c) down-regulation of c-myc transcripts; and (d) induction of tumor necrosis factor gene expression. This induction of monocytic differentiation was associated with transient increases in c-jun mRNA levels, which were maximal at 6 h. Similar effects were obtained for the c-fos gene. Run-on analysis demonstrated detectable levels of c-jun transcription in U-937 cells and that this rate is increased approximately 40-fold following okadaic acid exposure. c-jun mRNA levels were superinduced in cells treated with both okadaic acid and cycloheximide, whereas inhibition of protein synthesis had little, if any, effect on okadaic acid-induced c-jun transcription. The half-life of c-jun mRNA was similar (45-50 min) in both untreated and okadaic acid-induced cells. In contrast, treatment with both okadaic acid and cycloheximide was associated with stabilization (t 1/2 = 90 min) of c-jun transcripts. Taken together, these findings indicate that the induction of c-jun transcription by okadaic acid is controlled primarily by a transcriptional mechanism. Since previous studies have demonstrated that the c-jun gene is autoinduced by Jun/AP-1, we also studied transcription of c-jun promoter (positions -132/+170)-reporter gene constructs with and without a mutated AP-1 element. (ABSTRACT TRUNCATED AT 250 WORDS)\n" ], "offsets": [ [ 0, 1831 ] ] } ]

[ { "id": "PMID-1419903_T1", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 14, 19 ] ], "normalized": [] }, { "id": "PMID-1419903_T2", "type": "Protein", "text": [ "type 1" ], "offsets": [ [ 170, 176 ] ], "normalized": [] }, { "id": "PMID-1419903_T3", "type": "Protein", "text": [ "2A protein phosphatases" ], "offsets": [ [ 181, 204 ] ], "normalized": [] }, { "id": "PMID-1419903_T4", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 227, 232 ] ], "normalized": [] }, { "id": "PMID-1419903_T5", "type": "Protein", "text": [ "Mac-1 cell surface antigen" ], "offsets": [ [ 476, 502 ] ], "normalized": [] }, { "id": "PMID-1419903_T6", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 538, 543 ] ], "normalized": [] }, { "id": "PMID-1419903_T7", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 704, 709 ] ], "normalized": [] }, { "id": "PMID-1419903_T8", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 788, 793 ] ], "normalized": [] }, { "id": "PMID-1419903_T9", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 850, 855 ] ], "normalized": [] }, { "id": "PMID-1419903_T10", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 972, 977 ] ], "normalized": [] }, { "id": "PMID-1419903_T11", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1158, 1163 ] ], "normalized": [] }, { "id": "PMID-1419903_T12", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1196, 1201 ] ], "normalized": [] }, { "id": "PMID-1419903_T13", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1399, 1404 ] ], "normalized": [] }, { "id": "PMID-1419903_T14", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1480, 1485 ] ], "normalized": [] }, { "id": "PMID-1419903_T15", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1622, 1627 ] ], "normalized": [] }, { "id": "PMID-1419903_T16", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1694, 1699 ] ], "normalized": [] }, { "id": "PMID-1419903_T17", "type": "Entity", "text": [ "tumor necrosis factor gene" ], "offsets": [ [ 578, 604 ] ], "normalized": [] }, { "id": "PMID-1419903_T18", "type": "Entity", "text": [ "Jun/AP-1" ], "offsets": [ [ 1651, 1659 ] ], "normalized": [] }, { "id": "PMID-1419903_T19", "type": "Entity", "text": [ "AP-1 element" ], "offsets": [ [ 1783, 1795 ] ], "normalized": [] }, { "id": "PMID-1419903_T20", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 1783, 1787 ] ], "normalized": [] } ]

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[ { "id": "PMID-10364157__text", "type": "abstract", "text": [ "Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells. \nMalignant transformation usually inhibits terminal cell differentiation but the precise mechanisms involved are not understood. PU.1 is a hematopoietic-specific Ets family transcription factor that is required for development of some lymphoid and myeloid lineages. PU.1 can also act as an oncoprotein as activation of its expression in erythroid precursors by proviral insertion or transgenesis causes erythroleukemias in mice. Restoration of terminal differentiation in the mouse erythroleukemia (MEL) cells requires a decline in the level of PU.1, indicating that PU.1 can block erythroid differentiation. Here we investigate the mechanism by which PU.1 interferes with erythroid differentiation. We find that PU.1 interacts directly with GATA-1, a zinc finger transcription factor required for erythroid differentiation. Interaction between PU.1 and GATA-1 requires intact DNA-binding domains in both proteins. PU.1 represses GATA-1-mediated transcriptional activation. Both the DNA binding and transactivation domains of PU.1 are required for repression and both domains are also needed to block terminal differentiation in MEL cells. We also show that ectopic expression of PU.1 in Xenopus embryos is sufficient to block erythropoiesis during normal development. Furthermore, introduction of exogenous GATA-1 in both MEL cells and Xenopus embryos and explants relieves the block to erythroid differentiation imposed by PU.1. Our results indicate that the stoichiometry of directly interacting but opposing transcription factors may be a crucial determinant governing processes of normal differentiation and malignant transformation.\n" ], "offsets": [ [ 0, 1756 ] ] } ]

[ { "id": "PMID-10364157_T1", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 58, 62 ] ], "normalized": [] }, { "id": "PMID-10364157_T2", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 67, 73 ] ], "normalized": [] }, { "id": "PMID-10364157_T3", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 246, 250 ] ], "normalized": [] }, { "id": "PMID-10364157_T4", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 383, 387 ] ], "normalized": [] }, { "id": "PMID-10364157_T5", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 662, 666 ] ], "normalized": [] }, { "id": "PMID-10364157_T6", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 684, 688 ] ], "normalized": [] }, { "id": "PMID-10364157_T7", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 769, 773 ] ], "normalized": [] }, { "id": "PMID-10364157_T8", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 830, 834 ] ], "normalized": [] }, { "id": "PMID-10364157_T9", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 859, 865 ] ], "normalized": [] }, { "id": "PMID-10364157_T10", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 962, 966 ] ], "normalized": [] }, { "id": "PMID-10364157_T11", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 971, 977 ] ], "normalized": [] }, { "id": "PMID-10364157_T12", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1032, 1036 ] ], "normalized": [] }, { "id": "PMID-10364157_T13", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1047, 1053 ] ], "normalized": [] }, { "id": "PMID-10364157_T14", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1143, 1147 ] ], "normalized": [] }, { "id": "PMID-10364157_T15", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1297, 1301 ] ], "normalized": [] }, { "id": "PMID-10364157_T16", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1425, 1431 ] ], "normalized": [] }, { "id": "PMID-10364157_T17", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1542, 1546 ] ], "normalized": [] }, { "id": "PMID-10364157_T18", "type": "Entity", "text": [ "DNA-binding domains" ], "offsets": [ [ 994, 1013 ] ], "normalized": [] }, { "id": "PMID-10364157_T19", "type": "Entity", "text": [ "domains" ], "offsets": [ [ 1132, 1139 ] ], "normalized": [] } ]

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[ { "id": "PMID-10364157_R1", "type": "Protein-Component", "arg1_id": "PMID-10364157_T14", "arg2_id": "PMID-10364157_T19", "normalized": [] } ]

[ { "id": "PMID-9223506__text", "type": "abstract", "text": [ "Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for virus infectivity. \nWhen transcriptionally active, the human immunodeficiency virus (HIV) promoter contains a nucleosome-free region encompassing both the promoter/enhancer region and a large region (255 nucleotides [nt]) downstream of the transcription start site. We have previously identified new binding sites for transcription factors downstream of the transcription start site (nt 465 to 720): three AP-1 sites (I, II, and III), an AP3-like motif (AP3-L), a downstream binding factor (DBF) site, and juxtaposed Sp1 sites. Here, we show that the DBF site is an interferon-responsive factor (IRF) binding site and that the AP3-L motif binds the T-cell-specific factor NF-AT. Mutations that abolish the binding of each factor to its cognate site are introduced in an infectious HIV-1 molecular clone to study their effect on HIV-1 transcription and replication. Individual mutation of the DBF or AP3-L site as well as the double mutation AP-1(III)/AP3-L did not affect HIV-1 replication compared to that of the wild-type virus. In contrast, proviruses carrying mutations in the Sp1 sites were totally defective in terms of replication. Virus production occurred with slightly delayed kinetics for viruses containing combined mutations in the AP-1(III), AP3-L, and DBF sites and in the AP3-L and DBF-sites, whereas viruses mutated in the AP-1(I,II,III) and AP3-L sites and in the AP-1(I,II,III), AP3-L, and DBF sites exhibited a severely defective replicative phenotype. No RNA-packaging defect could be measured for any of the mutant viruses as determined by quantification of their HIV genomic RNA. Measurement of the transcriptional activity of the HIV-1 promoter after transient transfection of the HIV-1 provirus DNA or of long terminal repeat-luciferase constructs showed a positive correlation between the transcriptional and the replication defects for most mutants.\n" ], "offsets": [ [ 0, 2009 ] ] } ]

[ { "id": "PMID-9223506_T1", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 649, 652 ] ], "normalized": [] }, { "id": "PMID-9223506_T2", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1213, 1216 ] ], "normalized": [] }, { "id": "PMID-9223506_T3", "type": "Entity", "text": [ "Transcription factor binding sites" ], "offsets": [ [ 0, 34 ] ], "normalized": [] }, { "id": "PMID-9223506_T4", "type": "Entity", "text": [ "human immunodeficiency virus type 1 transcription start site" ], "offsets": [ [ 53, 113 ] ], "normalized": [] }, { "id": "PMID-9223506_T5", "type": "Entity", "text": [ "human immunodeficiency virus (HIV) promoter" ], "offsets": [ [ 187, 230 ] ], "normalized": [] }, { "id": "PMID-9223506_T6", "type": "Entity", "text": [ "nucleosome-free region" ], "offsets": [ [ 242, 264 ] ], "normalized": [] }, { "id": "PMID-9223506_T7", "type": "Entity", "text": [ "promoter/enhancer region" ], "offsets": [ [ 287, 311 ] ], "normalized": [] }, { "id": "PMID-9223506_T8", "type": "Entity", "text": [ "255 nucleotides" ], "offsets": [ [ 332, 347 ] ], "normalized": [] }, { "id": "PMID-9223506_T9", "type": "Entity", "text": [ "transcription start site" ], "offsets": [ [ 372, 396 ] ], "normalized": [] }, { "id": "PMID-9223506_T10", "type": "Entity", "text": [ "transcription start site" ], "offsets": [ [ 490, 514 ] ], "normalized": [] }, { "id": "PMID-9223506_T11", "type": "Entity", "text": [ "nt 465 to 720" ], "offsets": [ [ 516, 529 ] ], "normalized": [] }, { "id": "PMID-9223506_T12", "type": "Entity", "text": [ "AP-1 sites" ], "offsets": [ [ 538, 548 ] ], "normalized": [] }, { "id": "PMID-9223506_T13", "type": "Entity", "text": [ "AP3-like motif" ], "offsets": [ [ 570, 584 ] ], "normalized": [] }, { "id": "PMID-9223506_T14", "type": "Entity", "text": [ "AP3-L" ], "offsets": [ [ 586, 591 ] ], "normalized": [] }, { "id": "PMID-9223506_T15", "type": "Entity", "text": [ "downstream binding factor (DBF) site" ], "offsets": [ [ 596, 632 ] ], "normalized": [] }, { "id": "PMID-9223506_T16", "type": "Entity", "text": [ "sites" ], "offsets": [ [ 653, 658 ] ], "normalized": [] }, { "id": "PMID-9223506_T17", "type": "Entity", "text": [ "DBF site" ], "offsets": [ [ 683, 691 ] ], "normalized": [] }, { "id": "PMID-9223506_T18", "type": "Entity", "text": [ "interferon-responsive factor (IRF) binding site" ], "offsets": [ [ 698, 745 ] ], "normalized": [] }, { "id": "PMID-9223506_T19", "type": "Entity", "text": [ "AP3-L motif" ], "offsets": [ [ 759, 770 ] ], "normalized": [] }, { "id": "PMID-9223506_T20", "type": "Entity", "text": [ "site" ], "offsets": [ [ 1037, 1041 ] ], "normalized": [] }, { "id": "PMID-9223506_T21", "type": "Entity", "text": [ "mutation AP-1(III)/AP3-L" ], "offsets": [ [ 1064, 1088 ] ], "normalized": [] }, { "id": "PMID-9223506_T22", "type": "Entity", "text": [ "sites" ], "offsets": [ [ 1217, 1222 ] ], "normalized": [] }, { "id": "PMID-9223506_T23", "type": "Entity", "text": [ "sites" ], "offsets": [ [ 1403, 1408 ] ], "normalized": [] }, { "id": "PMID-9223506_T24", "type": "Entity", "text": [ "-sites" ], "offsets": [ [ 1433, 1439 ] ], "normalized": [] }, { "id": "PMID-9223506_T25", "type": "Entity", "text": [ "sites" ], "offsets": [ [ 1497, 1502 ] ], "normalized": [] }, { "id": "PMID-9223506_T26", "type": "Entity", "text": [ "sites" ], "offsets": [ [ 1545, 1550 ] ], "normalized": [] }, { "id": "PMID-9223506_T27", "type": "Entity", "text": [ "HIV-1 promoter" ], "offsets": [ [ 1786, 1800 ] ], "normalized": [] }, { "id": "PMID-9223506_T28", "type": "Entity", "text": [ "HIV-1 provirus DNA" ], "offsets": [ [ 1837, 1855 ] ], "normalized": [] }, { "id": "PMID-9223506_T29", "type": "Entity", "text": [ "long terminal repeat-luciferase constructs" ], "offsets": [ [ 1862, 1904 ] ], "normalized": [] } ]

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[ { "id": "PMID-9223506_R1", "type": "Protein-Component", "arg1_id": "PMID-9223506_T1", "arg2_id": "PMID-9223506_T16", "normalized": [] } ]

[ { "id": "PMID-9299590__text", "type": "abstract", "text": [ "The role of Rel/NF-kappa B proteins in viral oncogenesis and the regulation of viral transcription. \nRel/NF-kappa B is a ubiquitous transcription factor that consists of multiple polypeptide subunits, and is subject to complex regulatory mechanisms that involve protein-protein interactions, phosphorylation, ubiquitination, proteolytic degradation, and nucleocytoplasmic translocation. The sophisticated control of Rel/NF-kappa B activity is not surprising since this transcription factor is involved in a wide array of cellular responses to extracellular cues, associated with growth, development, apoptosis, and pathogen invasion. Thus, it is not unexpected that this versatile cellular homeostatic switch would be affected by a variety of viral pathogens, which have evolved mechanisms to utilize various aspects of Rel/NF-kappa B activity to facilitate their replication, cell survival and possibly evasion of immune responses. This review will cover the molecular mechanisms that are utilized by mammalian oncogenic viruses to affect the activity of Rel/NF-kappa B transcription factors and the role of Rel/NF-kappa B in the regulation of viral gene expression and replication.\n" ], "offsets": [ [ 0, 1184 ] ] } ]

[ { "id": "PMID-9299590_T1", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 16, 26 ] ], "normalized": [] }, { "id": "PMID-9299590_T2", "type": "Entity", "text": [ "Rel/NF-kappa B" ], "offsets": [ [ 101, 115 ] ], "normalized": [] }, { "id": "PMID-9299590_T3", "type": "Entity", "text": [ "ubiquitous transcription factor" ], "offsets": [ [ 121, 152 ] ], "normalized": [] }, { "id": "PMID-9299590_T4", "type": "Entity", "text": [ "Rel/NF-kappa B" ], "offsets": [ [ 416, 430 ] ], "normalized": [] }, { "id": "PMID-9299590_T5", "type": "Entity", "text": [ "Rel/NF-kappa B" ], "offsets": [ [ 820, 834 ] ], "normalized": [] }, { "id": "PMID-9299590_T6", "type": "Entity", "text": [ "Rel/NF-kappa B transcription factors" ], "offsets": [ [ 1056, 1092 ] ], "normalized": [] }, { "id": "PMID-9299590_T7", "type": "Entity", "text": [ "Rel/NF-kappa B" ], "offsets": [ [ 1109, 1123 ] ], "normalized": [] }, { "id": "PMID-9299590_T8", "type": "Entity", "text": [ "viral gene" ], "offsets": [ [ 1145, 1155 ] ], "normalized": [] } ]

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[ { "id": "PMID-9121455__text", "type": "abstract", "text": [ "Control of NFATx1 nuclear translocation by a calcineurin-regulated inhibitory domain. \nThe nuclear factor of activated T cells (NFAT) regulates cytokine gene expression in T cells through cis-acting elements located in the promoters of several cytokine genes. NFATx1, which is preferentially expressed in the thymus and peripheral blood leukocytes, is one of four members of the NFAT family of transcription factors. We have performed domain analysis of NFATx1 by examining the effects of deletion mutations. We found that NFATx1 DNA binding activity and interaction with AP-1 polypeptides were dependent on its central Rel similarity region and that transcriptional activation was reduced by deletions of either its N-terminal domain or its C-terminal domain, suggesting the presence of intrinsic transcriptional activation motifs in both regions. We also identified a potent inhibitory sequence within its N-terminal domain. We show that the inactivation of the inhibition was dependent on the activity of calcineurin, a calcium-calmodulin-dependent phosphatase. We also show that calcineurin associated with the N-terminal domain of NFATx1 at multiple docking sites and caused a reduction of size, indicative of dephosphorylation, in NFATx1. We have mapped the inhibitory activity to less than 60 residues, containing motifs that are conserved in all NFAT proteins. Finally, we demonstrate that deletion in NFATx1 of the mapped 60 residues leads to its nuclear translocation independent of calcium signaling. Our results support the model proposing that the N-terminal domain confers calcium-signaling dependence on NFATx1 transactivation activity by regulating its intracellular localization through a protein module that associates with calcineurin and is a target of its phosphatase activity.\n" ], "offsets": [ [ 0, 1799 ] ] } ]

[ { "id": "PMID-9121455_T1", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 11, 17 ] ], "normalized": [] }, { "id": "PMID-9121455_T2", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 260, 266 ] ], "normalized": [] }, { "id": "PMID-9121455_T3", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 454, 460 ] ], "normalized": [] }, { "id": "PMID-9121455_T4", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 523, 529 ] ], "normalized": [] }, { "id": "PMID-9121455_T5", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 1136, 1142 ] ], "normalized": [] }, { "id": "PMID-9121455_T6", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 1237, 1243 ] ], "normalized": [] }, { "id": "PMID-9121455_T7", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 1410, 1416 ] ], "normalized": [] }, { "id": "PMID-9121455_T8", "type": "Protein", "text": [ "NFATx1" ], "offsets": [ [ 1619, 1625 ] ], "normalized": [] }, { "id": "PMID-9121455_T9", "type": "Entity", "text": [ "calcineurin-regulated inhibitory domain" ], "offsets": [ [ 45, 84 ] ], "normalized": [] }, { "id": "PMID-9121455_T10", "type": "Entity", "text": [ "calcineurin" ], "offsets": [ [ 45, 56 ] ], "normalized": [] }, { "id": "PMID-9121455_T11", "type": "Entity", "text": [ "inhibitory domain" ], "offsets": [ [ 67, 84 ] ], "normalized": [] }, { "id": "PMID-9121455_T12", "type": "Entity", "text": [ "cytokine gene" ], "offsets": [ [ 144, 157 ] ], "normalized": [] }, { "id": "PMID-9121455_T13", "type": "Entity", "text": [ "cis-acting elements" ], "offsets": [ [ 188, 207 ] ], "normalized": [] }, { "id": "PMID-9121455_T14", "type": "Entity", "text": [ "promoters" ], "offsets": [ [ 223, 232 ] ], "normalized": [] }, { "id": "PMID-9121455_T15", "type": "Entity", "text": [ "cytokine genes" ], "offsets": [ [ 244, 258 ] ], "normalized": [] }, { "id": "PMID-9121455_T16", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 530, 533 ] ], "normalized": [] }, { "id": "PMID-9121455_T17", "type": "Entity", "text": [ "AP-1 polypeptides" ], "offsets": [ [ 572, 589 ] ], "normalized": [] }, { "id": "PMID-9121455_T18", "type": "Entity", "text": [ "central Rel similarity region" ], "offsets": [ [ 612, 641 ] ], "normalized": [] }, { "id": "PMID-9121455_T19", "type": "Entity", "text": [ "N-terminal domain" ], "offsets": [ [ 717, 734 ] ], "normalized": [] }, { "id": "PMID-9121455_T20", "type": "Entity", "text": [ "C-terminal domain" ], "offsets": [ [ 742, 759 ] ], "normalized": [] }, { "id": "PMID-9121455_T21", "type": "Entity", "text": [ "intrinsic transcriptional activation motifs" ], "offsets": [ [ 788, 831 ] ], "normalized": [] }, { "id": "PMID-9121455_T22", "type": "Entity", "text": [ "inhibitory sequence" ], "offsets": [ [ 877, 896 ] ], "normalized": [] }, { "id": "PMID-9121455_T23", "type": "Entity", "text": [ "N-terminal domain" ], "offsets": [ [ 908, 925 ] ], "normalized": [] }, { "id": "PMID-9121455_T24", "type": "Entity", "text": [ "calcineurin" ], "offsets": [ [ 1008, 1019 ] ], "normalized": [] }, { "id": "PMID-9121455_T25", "type": "Entity", "text": [ "calcineurin" ], "offsets": [ [ 1083, 1094 ] ], "normalized": [] }, { "id": "PMID-9121455_T26", "type": "Entity", "text": [ "N-terminal domain" ], "offsets": [ [ 1115, 1132 ] ], "normalized": [] }, { "id": "PMID-9121455_T27", "type": "Entity", "text": [ "multiple docking sites" ], "offsets": [ [ 1146, 1168 ] ], "normalized": [] }, { "id": "PMID-9121455_T28", "type": "Entity", "text": [ "60 residues" ], "offsets": [ [ 1297, 1308 ] ], "normalized": [] }, { "id": "PMID-9121455_T29", "type": "Entity", "text": [ "60 residues" ], "offsets": [ [ 1431, 1442 ] ], "normalized": [] }, { "id": "PMID-9121455_T30", "type": "Entity", "text": [ "N-terminal domain" ], "offsets": [ [ 1561, 1578 ] ], "normalized": [] }, { "id": "PMID-9121455_T31", "type": "Entity", "text": [ "protein module" ], "offsets": [ [ 1706, 1720 ] ], "normalized": [] }, { "id": "PMID-9121455_T32", "type": "Entity", "text": [ "calcineurin" ], "offsets": [ [ 1742, 1753 ] ], "normalized": [] } ]

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[]

[ { "id": "PMID-9121455_R1", "type": "Protein-Component", "arg1_id": "PMID-9121455_T4", "arg2_id": "PMID-9121455_T20", "normalized": [] }, { "id": "PMID-9121455_R2", "type": "Protein-Component", "arg1_id": "PMID-9121455_T4", "arg2_id": "PMID-9121455_T21", "normalized": [] }, { "id": "PMID-9121455_R3", "type": "Protein-Component", "arg1_id": "PMID-9121455_T4", "arg2_id": "PMID-9121455_T19", "normalized": [] }, { "id": "PMID-9121455_R4", "type": "Protein-Component", "arg1_id": "PMID-9121455_T4", "arg2_id": "PMID-9121455_T18", "normalized": [] }, { "id": "PMID-9121455_R5", "type": "Protein-Component", "arg1_id": "PMID-9121455_T5", "arg2_id": "PMID-9121455_T26", "normalized": [] }, { "id": "PMID-9121455_R6", "type": "Protein-Component", "arg1_id": "PMID-9121455_T7", "arg2_id": "PMID-9121455_T29", "normalized": [] } ]

[ { "id": "PMID-10358154__text", "type": "abstract", "text": [ "New immunosuppressive drug PNU156804 blocks IL-2-dependent proliferation and NF-kappa B and AP-1 activation. \nWe had previously shown that the drug undecylprodigiosin (UP) blocks human lymphocyte proliferation in vitro. We have now investigated the mechanism of action of a new analogue of UP, PNU156804, which shows a more favorable activity profile than UP in mice. We demonstrate here that the biological effect of PNU156804 in vitro is indistinguishable from UP: PNU156804 blocks human T cell proliferation in mid-late G1, as determined by cell cycle analysis, expression of cyclins, and cyclin-dependent kinases and retinoblastoma phosphorylation. In addition, we show that PNU156804 does not block significantly the induction of either IL-2 or IL-2R alpha- and gamma-chains but inhibits IL-2-dependent T cell proliferation. We have investigated several molecular pathways that are known to be activated by IL-2 in T cells. We show that PNU156804 does not inhibit c-myc and bcl-2 mRNA induction. On the other hand, PNU156804 efficiently inhibits the activation of the NF-kappa B and AP-1 transcription factors. PNU156804 inhibition of NF-kappa B activation is due to the inhibition of the degradation of I kappa B-alpha and I kappa B-beta. PNU156804 action is restricted to some signaling pathways; it does not affect NF-kappa B activation by PMA in T cells but blocks that induced by CD40 cross-linking in B lymphocytes. We conclude that the prodigiosin family of immunosuppressants is a new family of molecules that show a novel target specificity clearly distinct from that of other immunosuppressive drugs such as cyclosporin A, FK506, and rapamycin.\n" ], "offsets": [ [ 0, 1660 ] ] } ]

[ { "id": "PMID-10358154_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 44, 48 ] ], "normalized": [] }, { "id": "PMID-10358154_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 742, 746 ] ], "normalized": [] }, { "id": "PMID-10358154_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 793, 797 ] ], "normalized": [] }, { "id": "PMID-10358154_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 912, 916 ] ], "normalized": [] }, { "id": "PMID-10358154_T5", "type": "Protein", "text": [ "c-myc" ], "offsets": [ [ 969, 974 ] ], "normalized": [] }, { "id": "PMID-10358154_T6", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 979, 984 ] ], "normalized": [] }, { "id": "PMID-10358154_T7", "type": "Protein", "text": [ "I kappa B-alpha" ], "offsets": [ [ 1209, 1224 ] ], "normalized": [] }, { "id": "PMID-10358154_T8", "type": "Protein", "text": [ "I kappa B-beta" ], "offsets": [ [ 1229, 1243 ] ], "normalized": [] }, { "id": "PMID-10358154_T9", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 1390, 1394 ] ], "normalized": [] }, { "id": "PMID-10358154_T10", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 77, 87 ] ], "normalized": [] }, { "id": "PMID-10358154_T11", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 92, 96 ] ], "normalized": [] }, { "id": "PMID-10358154_T12", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1073, 1083 ] ], "normalized": [] }, { "id": "PMID-10358154_T13", "type": "Entity", "text": [ "AP-1 transcription factors" ], "offsets": [ [ 1088, 1114 ] ], "normalized": [] }, { "id": "PMID-10358154_T14", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1140, 1150 ] ], "normalized": [] }, { "id": "PMID-10358154_T15", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1323, 1333 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-1618911__text", "type": "abstract", "text": [ "Heterodimerization and transcriptional activation in vitro by NF-kappa B proteins. \nThe NF-kappa B family of transcription proteins represents multiple DNA binding, rel related polypeptides that contribute to regulation of genes involved in immune responsiveness and inflammation, as well as activation of the HIV long terminal repeat. In this study multiple NF-kappa B related polypeptides ranging from 85 to 45 kDa were examined for their capacity to interact with the PRDII regulatory element of interferon beta and were shown to possess distinct intrinsic DNA binding affinities for this NF-kappa B site and form multiple DNA binding homo- and heterodimer complexes in co-renaturation experiments. Furthermore, using DNA templates containing two copies of the PRDII domain linked to the rabbit beta globin gene, the purified polypeptides specifically stimulated NF-kappa B dependent transcription in an in vitro reconstitution assay as heterodimers but not as p50 homodimers. These experiments emphasize the role of NF-kappa B dimerization as a distinct level of transcriptional control that may permit functional diversification of a limited number of regulatory proteins.\n" ], "offsets": [ [ 0, 1178 ] ] } ]

[ { "id": "PMID-1618911_T1", "type": "Protein", "text": [ "rel" ], "offsets": [ [ 165, 168 ] ], "normalized": [] }, { "id": "PMID-1618911_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 964, 967 ] ], "normalized": [] }, { "id": "PMID-1618911_T3", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 152, 155 ] ], "normalized": [] }, { "id": "PMID-1618911_T4", "type": "Entity", "text": [ "genes" ], "offsets": [ [ 223, 228 ] ], "normalized": [] }, { "id": "PMID-1618911_T5", "type": "Entity", "text": [ "HIV long terminal repeat" ], "offsets": [ [ 310, 334 ] ], "normalized": [] }, { "id": "PMID-1618911_T6", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 359, 369 ] ], "normalized": [] }, { "id": "PMID-1618911_T7", "type": "Entity", "text": [ "PRDII regulatory element" ], "offsets": [ [ 471, 495 ] ], "normalized": [] }, { "id": "PMID-1618911_T8", "type": "Entity", "text": [ "interferon beta" ], "offsets": [ [ 499, 514 ] ], "normalized": [] }, { "id": "PMID-1618911_T9", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 560, 563 ] ], "normalized": [] }, { "id": "PMID-1618911_T10", "type": "Entity", "text": [ "NF-kappa B site" ], "offsets": [ [ 592, 607 ] ], "normalized": [] }, { "id": "PMID-1618911_T11", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 592, 602 ] ], "normalized": [] }, { "id": "PMID-1618911_T12", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 626, 629 ] ], "normalized": [] }, { "id": "PMID-1618911_T13", "type": "Entity", "text": [ "dimer complexes" ], "offsets": [ [ 654, 669 ] ], "normalized": [] }, { "id": "PMID-1618911_T14", "type": "Entity", "text": [ "PRDII domain" ], "offsets": [ [ 764, 776 ] ], "normalized": [] }, { "id": "PMID-1618911_T15", "type": "Entity", "text": [ "rabbit beta globin gene" ], "offsets": [ [ 791, 814 ] ], "normalized": [] }, { "id": "PMID-1618911_T16", "type": "Entity", "text": [ "purified polypeptides" ], "offsets": [ [ 820, 841 ] ], "normalized": [] }, { "id": "PMID-1618911_T17", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 866, 876 ] ], "normalized": [] }, { "id": "PMID-1618911_T18", "type": "Entity", "text": [ "homodimers" ], "offsets": [ [ 968, 978 ] ], "normalized": [] }, { "id": "PMID-1618911_T19", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1020, 1030 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-1618911_R1", "type": "Subunit-Complex", "arg1_id": "PMID-1618911_T2", "arg2_id": "PMID-1618911_T18", "normalized": [] } ]

[ { "id": "PMID-9862666__text", "type": "abstract", "text": [ "Nuclear factor of activated T cells and AP-1 are insufficient for IL-2 promoter activation: requirement for CD28 up-regulation of RE/AP. \nIL-2 gene transcription in T cells requires both TCR and costimulatory signals. IL-2 promoter activation in Jurkat T cells stimulated with superantigen presented by Raji B cells requires CD28 activation. The addition of rCTLA4Ig, which blocks CD28 binding to its ligand, to the cultures decreased IL-2 promoter activation by >80%. Interestingly, CTLA4Ig did not significantly inhibit the activation of either NF of activated T cells (NFAT) or AP-1 reporters. Therefore, activation of NFAT and AP-1 is insufficient for IL-2 promoter activation. In contrast, an RE/AP reporter was blocked by CTLA4Ig by >90%. Thus, the requirement for CD28 in IL-2 promoter activation appears to be due to RE/AP and not the NFAT or AP-1 sites. In addition, these data suggest that transcriptional activation of RE/AP is not mediated by NFAT, because activation of a NFAT reporter is not affected by the addition of CTLA4Ig.\n" ], "offsets": [ [ 0, 1043 ] ] } ]

[ { "id": "PMID-9862666_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 66, 70 ] ], "normalized": [] }, { "id": "PMID-9862666_T2", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 108, 112 ] ], "normalized": [] }, { "id": "PMID-9862666_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 138, 142 ] ], "normalized": [] }, { "id": "PMID-9862666_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 218, 222 ] ], "normalized": [] }, { "id": "PMID-9862666_T5", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 325, 329 ] ], "normalized": [] }, { "id": "PMID-9862666_T6", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 381, 385 ] ], "normalized": [] }, { "id": "PMID-9862666_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 435, 439 ] ], "normalized": [] }, { "id": "PMID-9862666_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 656, 660 ] ], "normalized": [] }, { "id": "PMID-9862666_T9", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 771, 775 ] ], "normalized": [] }, { "id": "PMID-9862666_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 779, 783 ] ], "normalized": [] }, { "id": "PMID-9862666_T11", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 40, 44 ] ], "normalized": [] }, { "id": "PMID-9862666_T12", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 71, 79 ] ], "normalized": [] }, { "id": "PMID-9862666_T13", "type": "Entity", "text": [ "RE/AP" ], "offsets": [ [ 130, 135 ] ], "normalized": [] }, { "id": "PMID-9862666_T14", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 223, 231 ] ], "normalized": [] }, { "id": "PMID-9862666_T15", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 440, 448 ] ], "normalized": [] }, { "id": "PMID-9862666_T16", "type": "Entity", "text": [ "AP-1 reporters" ], "offsets": [ [ 581, 595 ] ], "normalized": [] }, { "id": "PMID-9862666_T17", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 581, 585 ] ], "normalized": [] }, { "id": "PMID-9862666_T18", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 631, 635 ] ], "normalized": [] }, { "id": "PMID-9862666_T19", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 661, 669 ] ], "normalized": [] }, { "id": "PMID-9862666_T20", "type": "Entity", "text": [ "RE/AP reporter" ], "offsets": [ [ 698, 712 ] ], "normalized": [] }, { "id": "PMID-9862666_T21", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 784, 792 ] ], "normalized": [] }, { "id": "PMID-9862666_T22", "type": "Entity", "text": [ "sites" ], "offsets": [ [ 856, 861 ] ], "normalized": [] }, { "id": "PMID-9862666_T23", "type": "Entity", "text": [ "RE/AP" ], "offsets": [ [ 930, 935 ] ], "normalized": [] }, { "id": "PMID-9862666_T24", "type": "Entity", "text": [ "NFAT reporter" ], "offsets": [ [ 985, 998 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-9862666_R1", "type": "Protein-Component", "arg1_id": "PMID-9862666_T1", "arg2_id": "PMID-9862666_T12", "normalized": [] }, { "id": "PMID-9862666_R2", "type": "Protein-Component", "arg1_id": "PMID-9862666_T4", "arg2_id": "PMID-9862666_T14", "normalized": [] }, { "id": "PMID-9862666_R3", "type": "Protein-Component", "arg1_id": "PMID-9862666_T7", "arg2_id": "PMID-9862666_T15", "normalized": [] }, { "id": "PMID-9862666_R4", "type": "Protein-Component", "arg1_id": "PMID-9862666_T8", "arg2_id": "PMID-9862666_T19", "normalized": [] }, { "id": "PMID-9862666_R5", "type": "Protein-Component", "arg1_id": "PMID-9862666_T10", "arg2_id": "PMID-9862666_T21", "normalized": [] } ]

[ { "id": "PMID-8929546__text", "type": "abstract", "text": [ "Regulation of cytokine and cytokine receptor expression by glucocorticoids. \nGlucocorticoids (GCS) profoundly inhibit several aspects of T cell immunity largely through inhibition of cytokine expression at the transcriptional and posttranscriptional levels. GCS were also reported to act indirectly by inducing transforming growth factor-beta expression, which in turn blocks T cell immunity. In exerting their antiproliferative effects, GCS diffuse into target cells where they bind their cytoplasmic receptor, which in turn translocates to the nucleus where it inhibits transcription of cytokine genes through direct binding to the glucocorticoid response elements (GRE), which are located in the promoter region of cytokine genes or, alternatively, through antagonism of the action of transcription factors required for optimal transcriptional activation. In contrast to their inhibitory effects on cytokine expression, GCS up-regulate cytokine receptor expression that correlates with enhanced cytokine effects on target cells. In this review, we summarize the current state of knowledge of the mechanism of action of GCS, including the phenomenon of steroid-induced rebound, which ensues upon GCS withdrawal.\n" ], "offsets": [ [ 0, 1214 ] ] } ]

[ { "id": "PMID-8929546_T1", "type": "Protein", "text": [ "transforming growth factor-beta" ], "offsets": [ [ 311, 342 ] ], "normalized": [] }, { "id": "PMID-8929546_T2", "type": "Entity", "text": [ "cytokine genes" ], "offsets": [ [ 589, 603 ] ], "normalized": [] }, { "id": "PMID-8929546_T3", "type": "Entity", "text": [ "glucocorticoid response elements" ], "offsets": [ [ 634, 666 ] ], "normalized": [] }, { "id": "PMID-8929546_T4", "type": "Entity", "text": [ "GRE" ], "offsets": [ [ 668, 671 ] ], "normalized": [] }, { "id": "PMID-8929546_T5", "type": "Entity", "text": [ "cytokine genes" ], "offsets": [ [ 718, 732 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-10225377__text", "type": "abstract", "text": [ "Activation of nuclear factor-kappaB by lipopolysaccharide in mononuclear leukocytes is prevented by inhibitors of cytosolic phospholipase A2. \nIn monocytes, lipopolysaccharide induces synthesis and activity of the 85-kDa cytosolic phospholipase A2. This enzyme releases arachidonic acid and lyso-phospholipids from membranes which are metabolized to eicosanoids and platelet-activating-factor. These lipid mediators increase activity of transcription factors and expression of cytokine genes indicating a function for cytosolic phospholipase A2 in signal transduction and inflammation. We have shown previously that trifluoromethylketone inhibitors of cytosolic phospholipase A2 suppressed interleukin-1beta protein and steady-state mRNA levels in human lipopolysaccharide-stimulated peripheral blood mononuclear leukocytes. In this study, the subcellular mechanisms were analyzed by which trifluoromethylketones interfere with gene expression. We found that they reduced the initial interleukin-1beta mRNA transcription rate through prevention of degradation of inhibitor-kappaB alpha. Consequently, cytosolic activation, nuclear translocation and DNA-binding of nuclear factor-kappaB were decreased. Trifluoromethylketones ameliorate chronic inflammation in vivo. Thus, this therapeutic potency may reside in retention of inactive nuclear factor-kappaB in the cytosol thereby abrogating interleukin-1beta gene transcription.\n" ], "offsets": [ [ 0, 1427 ] ] } ]

[ { "id": "PMID-10225377_T1", "type": "Protein", "text": [ "interleukin-1beta" ], "offsets": [ [ 690, 707 ] ], "normalized": [] }, { "id": "PMID-10225377_T2", "type": "Protein", "text": [ "interleukin-1beta" ], "offsets": [ [ 984, 1001 ] ], "normalized": [] }, { "id": "PMID-10225377_T3", "type": "Protein", "text": [ "inhibitor-kappaB alpha" ], "offsets": [ [ 1063, 1085 ] ], "normalized": [] }, { "id": "PMID-10225377_T4", "type": "Protein", "text": [ "interleukin-1beta" ], "offsets": [ [ 1389, 1406 ] ], "normalized": [] }, { "id": "PMID-10225377_T5", "type": "Entity", "text": [ "nuclear factor-kappaB" ], "offsets": [ [ 14, 35 ] ], "normalized": [] }, { "id": "PMID-10225377_T6", "type": "Entity", "text": [ "cytokine genes" ], "offsets": [ [ 477, 491 ] ], "normalized": [] }, { "id": "PMID-10225377_T7", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 1149, 1152 ] ], "normalized": [] }, { "id": "PMID-10225377_T8", "type": "Entity", "text": [ "nuclear factor-kappaB" ], "offsets": [ [ 1164, 1185 ] ], "normalized": [] }, { "id": "PMID-10225377_T9", "type": "Entity", "text": [ "nuclear factor-kappaB" ], "offsets": [ [ 1333, 1354 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-9252117__text", "type": "abstract", "text": [ "EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes. \nEarly B cell factor (EBF) and E47 participate in the transcriptional control of early B lymphocyte differentiation. With the aim of identifying genetic targets for these transcription factors, we stably transfected cDNAs encoding EBF or a covalent homodimer of E47, individually or together, into immature hematopoietic Ba/F3 cells, which lack both factors. In combination, EBF and E47 induce efficient expression of the endogenous immunoglobulin surrogate light chain genes, lambda5 and VpreB, whereas other pre-B cell-specific genes remain silent. Multiple functionally important EBF and E47 binding sites were identified in the lambda5 promoter/enhancer region, indicating that lambda5 is a direct genetic target for these transcription factors. Taken together, these data suggest that EBF and E47 synergize to activate expression of a subset of genes that define an early stage of the B cell lineage.\n" ], "offsets": [ [ 0, 1013 ] ] } ]

[ { "id": "PMID-9252117_T1", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 0, 3 ] ], "normalized": [] }, { "id": "PMID-9252117_T2", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 8, 11 ] ], "normalized": [] }, { "id": "PMID-9252117_T3", "type": "Protein", "text": [ "Early B cell factor" ], "offsets": [ [ 108, 127 ] ], "normalized": [] }, { "id": "PMID-9252117_T4", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 129, 132 ] ], "normalized": [] }, { "id": "PMID-9252117_T5", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 138, 141 ] ], "normalized": [] }, { "id": "PMID-9252117_T6", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 338, 341 ] ], "normalized": [] }, { "id": "PMID-9252117_T7", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 369, 372 ] ], "normalized": [] }, { "id": "PMID-9252117_T8", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 482, 485 ] ], "normalized": [] }, { "id": "PMID-9252117_T9", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 490, 493 ] ], "normalized": [] }, { "id": "PMID-9252117_T10", "type": "Protein", "text": [ "lambda5" ], "offsets": [ [ 584, 591 ] ], "normalized": [] }, { "id": "PMID-9252117_T11", "type": "Protein", "text": [ "VpreB" ], "offsets": [ [ 596, 601 ] ], "normalized": [] }, { "id": "PMID-9252117_T12", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 690, 693 ] ], "normalized": [] }, { "id": "PMID-9252117_T13", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 698, 701 ] ], "normalized": [] }, { "id": "PMID-9252117_T14", "type": "Protein", "text": [ "lambda5" ], "offsets": [ [ 739, 746 ] ], "normalized": [] }, { "id": "PMID-9252117_T15", "type": "Protein", "text": [ "lambda5" ], "offsets": [ [ 789, 796 ] ], "normalized": [] }, { "id": "PMID-9252117_T16", "type": "Protein", "text": [ "EBF" ], "offsets": [ [ 897, 900 ] ], "normalized": [] }, { "id": "PMID-9252117_T17", "type": "Protein", "text": [ "E47" ], "offsets": [ [ 905, 908 ] ], "normalized": [] }, { "id": "PMID-9252117_T18", "type": "Entity", "text": [ "endogenous immunoglobulin surrogate light chain genes" ], "offsets": [ [ 52, 105 ] ], "normalized": [] }, { "id": "PMID-9252117_T19", "type": "Entity", "text": [ "covalent homodimer" ], "offsets": [ [ 347, 365 ] ], "normalized": [] }, { "id": "PMID-9252117_T20", "type": "Entity", "text": [ "endogenous immunoglobulin surrogate light chain genes" ], "offsets": [ [ 529, 582 ] ], "normalized": [] }, { "id": "PMID-9252117_T21", "type": "Entity", "text": [ "pre-B cell-specific genes" ], "offsets": [ [ 617, 642 ] ], "normalized": [] }, { "id": "PMID-9252117_T22", "type": "Entity", "text": [ "binding sites" ], "offsets": [ [ 702, 715 ] ], "normalized": [] }, { "id": "PMID-9252117_T23", "type": "Entity", "text": [ "promoter/enhancer region" ], "offsets": [ [ 747, 771 ] ], "normalized": [] }, { "id": "PMID-9252117_T24", "type": "Entity", "text": [ "genes" ], "offsets": [ [ 957, 962 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-9252117_1", "entity_ids": [ "PMID-9252117_T3", "PMID-9252117_T4" ] } ]

[ { "id": "PMID-9252117_R1", "type": "Subunit-Complex", "arg1_id": "PMID-9252117_T7", "arg2_id": "PMID-9252117_T19", "normalized": [] }, { "id": "PMID-9252117_R2", "type": "Protein-Component", "arg1_id": "PMID-9252117_T14", "arg2_id": "PMID-9252117_T22", "normalized": [] }, { "id": "PMID-9252117_R3", "type": "Protein-Component", "arg1_id": "PMID-9252117_T14", "arg2_id": "PMID-9252117_T23", "normalized": [] } ]

[ { "id": "PMID-8428966__text", "type": "abstract", "text": [ "Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells (NF-AT) complex. \nThe lymphoid-specific transcription complex, NF-AT, is involved in early gene activation in T cells and is assembled from a pre-existing, T cell restricted cytoplasmic factor and an inducible ubiquitous nuclear component within 30 min after activation through the antigen receptor. Recent studies have implicated the family of AP1 factors as components of the murine NF-AT complex. Evidence is provided here that the nuclear component of human NF-AT contains the phorbol ester-inducible transcription factor AP1 (Jun/Fos). We further characterize which AP1 family members can assume this role. Antisera to Fos inhibits NF-AT DNA binding as does an oligonucleotide containing a binding site for AP1. Constitutive expression in vivo of Fos, and to a lesser extent Fra-1, eliminates the requirement for phorbol 12-myristate 13-acetate (PMA) stimulation, leaving NF-AT-directed transcription responsive to calcium ionophore alone. Overexpression of cJun or JunD, but not JunB, also eliminates the requirement for PMA, indicating that many but not all Jun- and Fos-related proteins functionally activate NF-AT-dependent transcription in the presence of the cytoplasmic component. NF-AT DNA binding can be reconstituted in vitro using semi-purified AP1 proteins mixed with cytosol from T lymphocytes. Fos proteins are not needed for this reconstitution, and although JunB is not functional, it can participate in the NF-AT DNA binding complex. Finally, we have partially purified the cytoplasmic component of NF-AT and show by elution and renaturation from SDS-polyacrylamide gel electrophoresis gels that it has a molecular mass between 94 and 116 kDa and may have multiple differentially modified forms.\n" ], "offsets": [ [ 0, 1838 ] ] } ]

[ { "id": "PMID-8428966_T1", "type": "Protein", "text": [ "Fra-1" ], "offsets": [ [ 900, 905 ] ], "normalized": [] }, { "id": "PMID-8428966_T2", "type": "Protein", "text": [ "cJun" ], "offsets": [ [ 1083, 1087 ] ], "normalized": [] }, { "id": "PMID-8428966_T3", "type": "Protein", "text": [ "JunD" ], "offsets": [ [ 1091, 1095 ] ], "normalized": [] }, { "id": "PMID-8428966_T4", "type": "Protein", "text": [ "JunB" ], "offsets": [ [ 1105, 1109 ] ], "normalized": [] }, { "id": "PMID-8428966_T5", "type": "Protein", "text": [ "JunB" ], "offsets": [ [ 1499, 1503 ] ], "normalized": [] }, { "id": "PMID-8428966_T6", "type": "Entity", "text": [ "nuclear factor of activated T cells (NF-AT) complex" ], "offsets": [ [ 84, 135 ] ], "normalized": [] }, { "id": "PMID-8428966_T7", "type": "Entity", "text": [ "transcription complex, NF-AT" ], "offsets": [ [ 160, 188 ] ], "normalized": [] }, { "id": "PMID-8428966_T8", "type": "Entity", "text": [ "early gene" ], "offsets": [ [ 205, 215 ] ], "normalized": [] }, { "id": "PMID-8428966_T9", "type": "Entity", "text": [ "murine NF-AT complex" ], "offsets": [ [ 498, 518 ] ], "normalized": [] }, { "id": "PMID-8428966_T10", "type": "Entity", "text": [ "human NF-AT" ], "offsets": [ [ 576, 587 ] ], "normalized": [] }, { "id": "PMID-8428966_T11", "type": "Entity", "text": [ "phorbol ester-inducible transcription factor AP1" ], "offsets": [ [ 601, 649 ] ], "normalized": [] }, { "id": "PMID-8428966_T12", "type": "Entity", "text": [ "Jun/Fos" ], "offsets": [ [ 651, 658 ] ], "normalized": [] }, { "id": "PMID-8428966_T13", "type": "Entity", "text": [ "NF-AT" ], "offsets": [ [ 757, 762 ] ], "normalized": [] }, { "id": "PMID-8428966_T14", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 763, 766 ] ], "normalized": [] }, { "id": "PMID-8428966_T15", "type": "Entity", "text": [ "oligonucleotide" ], "offsets": [ [ 786, 801 ] ], "normalized": [] }, { "id": "PMID-8428966_T16", "type": "Entity", "text": [ "binding site for AP1" ], "offsets": [ [ 815, 835 ] ], "normalized": [] }, { "id": "PMID-8428966_T17", "type": "Entity", "text": [ "AP1" ], "offsets": [ [ 832, 835 ] ], "normalized": [] }, { "id": "PMID-8428966_T18", "type": "Entity", "text": [ "NF-AT" ], "offsets": [ [ 997, 1002 ] ], "normalized": [] }, { "id": "PMID-8428966_T19", "type": "Entity", "text": [ "NF-AT" ], "offsets": [ [ 1237, 1242 ] ], "normalized": [] }, { "id": "PMID-8428966_T20", "type": "Entity", "text": [ "NF-AT" ], "offsets": [ [ 1313, 1318 ] ], "normalized": [] }, { "id": "PMID-8428966_T21", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 1319, 1322 ] ], "normalized": [] }, { "id": "PMID-8428966_T22", "type": "Entity", "text": [ "NF-AT" ], "offsets": [ [ 1549, 1554 ] ], "normalized": [] }, { "id": "PMID-8428966_T23", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 1555, 1558 ] ], "normalized": [] }, { "id": "PMID-8428966_T24", "type": "Entity", "text": [ "NF-AT" ], "offsets": [ [ 1641, 1646 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-7892566__text", "type": "abstract", "text": [ "[Regulation of transcription of the interleukin-2 gene in B-lymphocytes] \nSince most B cell clones immortalized with EBV virus can be induced to produce interleukin-2, a typical T cell cytokine, we studied the role of different elements of the IL-2 promoter in such clones by transfection. It was found, in particular, that the element TCEd, which binds the transcription factor NF-kB, is very active in all three B clones tested. This element has no activity in T cells of the Jurkat line. The NFATd element, which binds the transcription factor NFAT-1 and is very active in T cells, is only weakly active in one B clone and not at all in another. Different elements thus contribute to IL-2 promoter activity in different cells.\n" ], "offsets": [ [ 0, 730 ] ] } ]

[ { "id": "PMID-7892566_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 36, 49 ] ], "normalized": [] }, { "id": "PMID-7892566_T2", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 153, 166 ] ], "normalized": [] }, { "id": "PMID-7892566_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 244, 248 ] ], "normalized": [] }, { "id": "PMID-7892566_T4", "type": "Protein", "text": [ "NFAT-1" ], "offsets": [ [ 547, 553 ] ], "normalized": [] }, { "id": "PMID-7892566_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 687, 691 ] ], "normalized": [] }, { "id": "PMID-7892566_T6", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 249, 257 ] ], "normalized": [] }, { "id": "PMID-7892566_T7", "type": "Entity", "text": [ "TCEd" ], "offsets": [ [ 336, 340 ] ], "normalized": [] }, { "id": "PMID-7892566_T8", "type": "Entity", "text": [ "transcription factor NF-kB" ], "offsets": [ [ 358, 384 ] ], "normalized": [] }, { "id": "PMID-7892566_T9", "type": "Entity", "text": [ "NFATd element" ], "offsets": [ [ 495, 508 ] ], "normalized": [] }, { "id": "PMID-7892566_T10", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 692, 700 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-7892566_R1", "type": "Protein-Component", "arg1_id": "PMID-7892566_T3", "arg2_id": "PMID-7892566_T6", "normalized": [] }, { "id": "PMID-7892566_R2", "type": "Protein-Component", "arg1_id": "PMID-7892566_T5", "arg2_id": "PMID-7892566_T10", "normalized": [] } ]

[ { "id": "PMID-8977228__text", "type": "abstract", "text": [ "The state of maturation of monocytes into macrophages determines the effects of IL-4 and IL-13 on HIV replication. \nThe molecular mechanisms of the effects of IL-4 and IL-13 on HIV infection in human monocytes as they matured into monocyte-derived macrophages over 7 days were investigated using HIV-1(BaL), and low passage clinical strains. IL-4 and IL-13 up-regulated the expression of both genomic and spliced HIV mRNA in monocytes cultured on Teflon, as determined by Northern analysis and p24 Ag assay. Using a nuclear run-on assay, IL-4 stimulation was shown to enhance transcription by two- to threefold. IL-4 stimulated nuclear factor-kappaB nuclear translocation and binding before enhancement of HIV RNA expression. Conversely, IL-4 and IL-13 markedly and significantly inhibited HIV replication at the transcriptional level in monocyte-derived macrophages, and this occurred whether these cytokines were added before or after HIV infection. The reversal from stimulation to inhibition occurred after 3 to 5 days of adherence to plastic. IL-4 had no significant effect on HIV reverse transcription. The effect of both cytokines on the monocyte maturation/differentiation (CD11b, CD13, and CD26) and other macrophage markers (CD14 and CD68) was examined. IL-4 enhanced CD11b, but inhibited CD26 expression and delayed CD13 loss. IL-13 had similar effects on CD11b and CD13, but no effect on CD26. Hence, these cytokines do not simply enhance monocyte differentiation, but have complex and slightly divergent effects that impact on HIV replication probably through cell signaling pathways and nuclear factor-kappaB translocation.\n" ], "offsets": [ [ 0, 1638 ] ] } ]

[ { "id": "PMID-8977228_T1", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 80, 84 ] ], "normalized": [] }, { "id": "PMID-8977228_T2", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 89, 94 ] ], "normalized": [] }, { "id": "PMID-8977228_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 159, 163 ] ], "normalized": [] }, { "id": "PMID-8977228_T4", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 168, 173 ] ], "normalized": [] }, { "id": "PMID-8977228_T5", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 342, 346 ] ], "normalized": [] }, { "id": "PMID-8977228_T6", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 351, 356 ] ], "normalized": [] }, { "id": "PMID-8977228_T7", "type": "Protein", "text": [ "p24 Ag" ], "offsets": [ [ 494, 500 ] ], "normalized": [] }, { "id": "PMID-8977228_T8", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 538, 542 ] ], "normalized": [] }, { "id": "PMID-8977228_T9", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 612, 616 ] ], "normalized": [] }, { "id": "PMID-8977228_T10", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 738, 742 ] ], "normalized": [] }, { "id": "PMID-8977228_T11", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 747, 752 ] ], "normalized": [] }, { "id": "PMID-8977228_T12", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1048, 1052 ] ], "normalized": [] }, { "id": "PMID-8977228_T13", "type": "Protein", "text": [ "CD11b" ], "offsets": [ [ 1182, 1187 ] ], "normalized": [] }, { "id": "PMID-8977228_T14", "type": "Protein", "text": [ "CD13" ], "offsets": [ [ 1189, 1193 ] ], "normalized": [] }, { "id": "PMID-8977228_T15", "type": "Protein", "text": [ "CD26" ], "offsets": [ [ 1199, 1203 ] ], "normalized": [] }, { "id": "PMID-8977228_T16", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1235, 1239 ] ], "normalized": [] }, { "id": "PMID-8977228_T17", "type": "Protein", "text": [ "CD68" ], "offsets": [ [ 1244, 1248 ] ], "normalized": [] }, { "id": "PMID-8977228_T18", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1264, 1268 ] ], "normalized": [] }, { "id": "PMID-8977228_T19", "type": "Protein", "text": [ "CD11b" ], "offsets": [ [ 1278, 1283 ] ], "normalized": [] }, { "id": "PMID-8977228_T20", "type": "Protein", "text": [ "CD26" ], "offsets": [ [ 1299, 1303 ] ], "normalized": [] }, { "id": "PMID-8977228_T21", "type": "Protein", "text": [ "CD13" ], "offsets": [ [ 1327, 1331 ] ], "normalized": [] }, { "id": "PMID-8977228_T22", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 1338, 1343 ] ], "normalized": [] }, { "id": "PMID-8977228_T23", "type": "Protein", "text": [ "CD11b" ], "offsets": [ [ 1367, 1372 ] ], "normalized": [] }, { "id": "PMID-8977228_T24", "type": "Protein", "text": [ "CD13" ], "offsets": [ [ 1377, 1381 ] ], "normalized": [] }, { "id": "PMID-8977228_T25", "type": "Protein", "text": [ "CD26" ], "offsets": [ [ 1400, 1404 ] ], "normalized": [] }, { "id": "PMID-8977228_T26", "type": "Entity", "text": [ "nuclear factor-kappaB" ], "offsets": [ [ 628, 649 ] ], "normalized": [] }, { "id": "PMID-8977228_T27", "type": "Entity", "text": [ "nuclear factor-kappaB" ], "offsets": [ [ 1601, 1622 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-9317151__text", "type": "abstract", "text": [ "Dual effects of LPS antibodies on cellular uptake of LPS and LPS-induced proinflammatory functions. \nHuman phagocytes recognize bacterial LPS (endotoxin) through membrane CD14 (mCD14), a proinflammatory LPS receptor. This study tested the hypothesis that anti-LPS Abs neutralize endotoxin by blocking cellular uptake through mCD14. Ab-associated changes in the uptake and cellular distribution of FITC-LPS were assessed by flow cytometry and laser scanning confocal microscopy in human CD14-transfected Chinese hamster ovary fibroblasts (CHO-CD14 cells) and human peripheral blood monocytes. LPS core- and O-side chain-specific mAbs inhibited mCD14-mediated LPS uptake by both cell types in the presence of serum. O-side chain-specific mAb concurrently enhanced complement-dependent LPS uptake by monocytes through complement receptor-1 (CR1) and uptake by CHO-CD14 cells involving another heat-labile serum factor(s) and cell-associated recognition molecule(s). Core-specific mAb inhibited mCD14-mediated uptake of homologous and heterologous LPS, while producing less concurrent enhancement of non-mCD14-mediated LPS uptake. The modulation by anti-LPS mAbs of mCD14-mediated LPS uptake was associated with inhibition of LPS-induced nuclear factor-kappaB (NF-kappaB) translocation and TNF-alpha secretion in CHO-CD14 cells and monocytes, respectively, while mAb enhancement of non-mCD14-mediated LPS uptake stimulated these activities. LPS-specific Abs thus mediate anti-inflammatory and proinflammatory functions, respectively, by preventing target cell uptake of LPS through mCD14 and augmenting uptake through CR1 or other cell receptors.\n" ], "offsets": [ [ 0, 1643 ] ] } ]

[ { "id": "PMID-9317151_T1", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 171, 175 ] ], "normalized": [] }, { "id": "PMID-9317151_T2", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 177, 182 ] ], "normalized": [] }, { "id": "PMID-9317151_T3", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 325, 330 ] ], "normalized": [] }, { "id": "PMID-9317151_T4", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 486, 490 ] ], "normalized": [] }, { "id": "PMID-9317151_T5", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 542, 546 ] ], "normalized": [] }, { "id": "PMID-9317151_T6", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 643, 648 ] ], "normalized": [] }, { "id": "PMID-9317151_T7", "type": "Protein", "text": [ "complement receptor-1" ], "offsets": [ [ 815, 836 ] ], "normalized": [] }, { "id": "PMID-9317151_T8", "type": "Protein", "text": [ "CR1" ], "offsets": [ [ 838, 841 ] ], "normalized": [] }, { "id": "PMID-9317151_T9", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 861, 865 ] ], "normalized": [] }, { "id": "PMID-9317151_T10", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 991, 996 ] ], "normalized": [] }, { "id": "PMID-9317151_T11", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 1100, 1105 ] ], "normalized": [] }, { "id": "PMID-9317151_T12", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 1162, 1167 ] ], "normalized": [] }, { "id": "PMID-9317151_T13", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1286, 1295 ] ], "normalized": [] }, { "id": "PMID-9317151_T14", "type": "Protein", "text": [ "CD14" ], "offsets": [ [ 1313, 1317 ] ], "normalized": [] }, { "id": "PMID-9317151_T15", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 1382, 1387 ] ], "normalized": [] }, { "id": "PMID-9317151_T16", "type": "Protein", "text": [ "mCD14" ], "offsets": [ [ 1578, 1583 ] ], "normalized": [] }, { "id": "PMID-9317151_T17", "type": "Protein", "text": [ "CR1" ], "offsets": [ [ 1614, 1617 ] ], "normalized": [] }, { "id": "PMID-9317151_T18", "type": "Entity", "text": [ "nuclear factor-kappaB" ], "offsets": [ [ 1234, 1255 ] ], "normalized": [] }, { "id": "PMID-9317151_T19", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1257, 1266 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-9317151_1", "entity_ids": [ "PMID-9317151_T1", "PMID-9317151_T2" ] }, { "id": "PMID-9317151_2", "entity_ids": [ "PMID-9317151_T7", "PMID-9317151_T8" ] } ]

[]

[ { "id": "PMID-9712026__text", "type": "abstract", "text": [ "A CD28-associated signaling pathway leading to cytokine gene transcription and T cell proliferation without TCR engagement. \nStimulation of resting human T cells with the CD28-specific mAb BW 828 induces proliferation and cytokine synthesis without further requirement for TCR coengagement. This observation prompted us to postulate that signal 2 (costimulatory signal) alone without signal 1 (TCR signal) can activate T cells. To test whether this putative function of CD28 is mediated via a particular signaling pathway, we compared early signaling events initiated in resting T cells by the stimulatory mAb BW 828 with signals triggered by the nonstimulating CD28 mAb 9.3. Stimulation of T cells with BW 828 induced an increase in intracellular Ca2+, but did not lead to detectable activation of the protein kinases p56(lck) and c-Raf-1. This pathway resulted in the induction of the transcription factors NF-kappa B, NF-AT, and proteins binding to the CD28 response element of the IL-2 promoter. On the other hand, stimulation of T cells with mAb 9.3 increased the level of intracellular Ca2+ and triggered the activation of p56(lck) and c-Raf-1, but was unable to induce the binding of transcription factors to the IL-2 promoter. In contrast to the differential signaling of BW 828 and 9.3 in resting T cells, the two mAbs exhibited a similar pattern of early signaling events in activated T cells and Jurkat cells (p56(lck) activation, association of phosphatidylinositol 3-kinase with CD28), indicating that the signaling capacity of CD28 changes with activation. These data support the view that stimulation through CD28 can induce some effector functions in T cells and suggest that this capacity is associated with a particular pattern of early signaling events.\n" ], "offsets": [ [ 0, 1773 ] ] } ]

[ { "id": "PMID-9712026_T1", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 2, 6 ] ], "normalized": [] }, { "id": "PMID-9712026_T2", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 171, 175 ] ], "normalized": [] }, { "id": "PMID-9712026_T3", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 470, 474 ] ], "normalized": [] }, { "id": "PMID-9712026_T4", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 662, 666 ] ], "normalized": [] }, { "id": "PMID-9712026_T5", "type": "Protein", "text": [ "p56(lck)" ], "offsets": [ [ 819, 827 ] ], "normalized": [] }, { "id": "PMID-9712026_T6", "type": "Protein", "text": [ "c-Raf-1" ], "offsets": [ [ 832, 839 ] ], "normalized": [] }, { "id": "PMID-9712026_T7", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 956, 960 ] ], "normalized": [] }, { "id": "PMID-9712026_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 985, 989 ] ], "normalized": [] }, { "id": "PMID-9712026_T9", "type": "Protein", "text": [ "p56(lck)" ], "offsets": [ [ 1129, 1137 ] ], "normalized": [] }, { "id": "PMID-9712026_T10", "type": "Protein", "text": [ "c-Raf-1" ], "offsets": [ [ 1142, 1149 ] ], "normalized": [] }, { "id": "PMID-9712026_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1220, 1224 ] ], "normalized": [] }, { "id": "PMID-9712026_T12", "type": "Protein", "text": [ "BW 828" ], "offsets": [ [ 1280, 1286 ] ], "normalized": [] }, { "id": "PMID-9712026_T13", "type": "Protein", "text": [ "9.3" ], "offsets": [ [ 1291, 1294 ] ], "normalized": [] }, { "id": "PMID-9712026_T14", "type": "Protein", "text": [ "p56(lck)" ], "offsets": [ [ 1421, 1429 ] ], "normalized": [] }, { "id": "PMID-9712026_T15", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1492, 1496 ] ], "normalized": [] }, { "id": "PMID-9712026_T16", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1541, 1545 ] ], "normalized": [] }, { "id": "PMID-9712026_T17", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1624, 1628 ] ], "normalized": [] }, { "id": "PMID-9712026_T18", "type": "Entity", "text": [ "cytokine gene" ], "offsets": [ [ 47, 60 ] ], "normalized": [] }, { "id": "PMID-9712026_T19", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 909, 919 ] ], "normalized": [] }, { "id": "PMID-9712026_T20", "type": "Entity", "text": [ "response element" ], "offsets": [ [ 961, 977 ] ], "normalized": [] }, { "id": "PMID-9712026_T21", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 990, 998 ] ], "normalized": [] }, { "id": "PMID-9712026_T22", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1225, 1233 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-9712026_R1", "type": "Protein-Component", "arg1_id": "PMID-9712026_T8", "arg2_id": "PMID-9712026_T20", "normalized": [] }, { "id": "PMID-9712026_R2", "type": "Protein-Component", "arg1_id": "PMID-9712026_T8", "arg2_id": "PMID-9712026_T21", "normalized": [] }, { "id": "PMID-9712026_R3", "type": "Protein-Component", "arg1_id": "PMID-9712026_T11", "arg2_id": "PMID-9712026_T22", "normalized": [] } ]

[ { "id": "PMID-8158122__text", "type": "abstract", "text": [ "Activation of nuclear factor kappa B in human neuroblastoma cell lines. \nThe nuclear factor kappa B (NF-kappa B) is a eukaryotic transcription factor. In B cells and macrophages it is constitutively present in cell nuclei, whereas in many other cell types, NF-kappa B translocates from cytosol to nucleus as a result of transduction by tumor necrosis factor alpha (TNF alpha), phorbol ester, and other polyclonal signals. Using neuroblastoma cell lines as models, we have shown that in neural cells NF-kappa B was present in the cytosol and translocated into nuclei as a result of TNF alpha treatment. The TNF alpha-activated NF-kappa B was transcriptionally functional. NF-kappa B activation by TNF alpha was not correlated with cell differentiation or proliferation. However, reagents such as nerve growth factor (NGF) and the phorbol ester phorbol 12-myristate 13-acetate (PMA), which induce phenotypical differentiation of the SH-SY5Y neuroblastoma cell line, activated NF-kappa B, but only in that particular cell line. In a NGF-responsive rat pheochromocytoma cell line, PC12, PMA activated NF-kappa B, whereas NGF did not. In other neuroblastoma cell lines, such as SK-N-Be(2), the lack of PMA induction of differentiation was correlated with the lack of NF-kappa B activation. We found, moreover, that in SK-N-Be(2) cells protein kinase C (PKC) enzymatic activity was much lower compared with that in a control cell line and that the low PKC enzymatic activity was due to low PKC protein expression. NF-kappa B was not activated by retinoic acid, which induced morphological differentiation of all the neuroblastoma cell lines used in the present study. Thus, NF-kappa B activation was not required for neuroblastoma cell differentiation. Furthermore, the results obtained with TNF alpha proved that NF-kappa B activation was not sufficient for induction of neuroblastoma differentiation.\n" ], "offsets": [ [ 0, 1897 ] ] } ]

[ { "id": "PMID-8158122_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 336, 363 ] ], "normalized": [] }, { "id": "PMID-8158122_T2", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 365, 374 ] ], "normalized": [] }, { "id": "PMID-8158122_T3", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 581, 590 ] ], "normalized": [] }, { "id": "PMID-8158122_T4", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 606, 615 ] ], "normalized": [] }, { "id": "PMID-8158122_T5", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 696, 705 ] ], "normalized": [] }, { "id": "PMID-8158122_T6", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 1786, 1795 ] ], "normalized": [] }, { "id": "PMID-8158122_T7", "type": "Entity", "text": [ "nuclear factor kappa B" ], "offsets": [ [ 14, 36 ] ], "normalized": [] }, { "id": "PMID-8158122_T8", "type": "Entity", "text": [ "nuclear factor kappa B" ], "offsets": [ [ 77, 99 ] ], "normalized": [] }, { "id": "PMID-8158122_T9", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 101, 111 ] ], "normalized": [] }, { "id": "PMID-8158122_T10", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 257, 267 ] ], "normalized": [] }, { "id": "PMID-8158122_T11", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 499, 509 ] ], "normalized": [] }, { "id": "PMID-8158122_T12", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 626, 636 ] ], "normalized": [] }, { "id": "PMID-8158122_T13", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 671, 681 ] ], "normalized": [] }, { "id": "PMID-8158122_T14", "type": "Entity", "text": [ "nerve growth factor" ], "offsets": [ [ 795, 814 ] ], "normalized": [] }, { "id": "PMID-8158122_T15", "type": "Entity", "text": [ "NGF" ], "offsets": [ [ 816, 819 ] ], "normalized": [] }, { "id": "PMID-8158122_T16", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 974, 984 ] ], "normalized": [] }, { "id": "PMID-8158122_T17", "type": "Entity", "text": [ "NGF" ], "offsets": [ [ 1030, 1033 ] ], "normalized": [] }, { "id": "PMID-8158122_T18", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1097, 1107 ] ], "normalized": [] }, { "id": "PMID-8158122_T19", "type": "Entity", "text": [ "NGF" ], "offsets": [ [ 1117, 1120 ] ], "normalized": [] }, { "id": "PMID-8158122_T20", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1262, 1272 ] ], "normalized": [] }, { "id": "PMID-8158122_T21", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1508, 1518 ] ], "normalized": [] }, { "id": "PMID-8158122_T22", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1668, 1678 ] ], "normalized": [] }, { "id": "PMID-8158122_T23", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1808, 1818 ] ], "normalized": [] } ]

[]

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[]

[ { "id": "PMID-8663022__text", "type": "abstract", "text": [ "Octamer binding factors and their coactivator can activate the murine PU.1 (spi-1) promoter. \nPU.1 (spi-1), a member of the Ets transcription factor family, is predominantly expressed in myeloid and B cells, activates many B cell and myeloid genes, and is critical for development of both of these lineages. Our previous studies (Chen, H.M., Ray-Gallet, D., Zhang, P., Hetherington, C.J., Gonzalez, D.A., Zhang, D.-E., Moreau-Gachelin, F., and Tenen, D.G.(1995) Oncogene 11, 1549-1560) demonstrate that the PU.1 promoter directs cell type-specific reporter gene expression in myeloid cell lines, and that PU.1 activates its own promoter in an autoregulatory loop. Here we show that the murine PU.1 promoter is also specifically and highly functional in B cell lines as well. Oct-1 and Oct-2 can bind specifically to a site at base pair -55 in vitro, and this site is specifically protected in B cells in vivo. We also demonstrate that two other sites contribute to promoter activity in B cells; an Sp1 binding site adjacent to the octamer site, and the PU.1 autoregulatory site. Finally, we show that the B cell coactivator OBF-1/Bob1/OCA-B is only expressed in B cells and not in myeloid cells, and that OBF-1/Bob1/OCA-B can transactivate the PU.1 promoter in HeLa and myeloid cells. This B cell restricted coactivator may be responsible for the B cell specific expression of PU.1 mediated by the octamer site.\n" ], "offsets": [ [ 0, 1412 ] ] } ]

[ { "id": "PMID-8663022_T1", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 70, 74 ] ], "normalized": [] }, { "id": "PMID-8663022_T2", "type": "Protein", "text": [ "spi-1" ], "offsets": [ [ 76, 81 ] ], "normalized": [] }, { "id": "PMID-8663022_T3", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 94, 98 ] ], "normalized": [] }, { "id": "PMID-8663022_T4", "type": "Protein", "text": [ "spi-1" ], "offsets": [ [ 100, 105 ] ], "normalized": [] }, { "id": "PMID-8663022_T5", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 507, 511 ] ], "normalized": [] }, { "id": "PMID-8663022_T6", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 605, 609 ] ], "normalized": [] }, { "id": "PMID-8663022_T7", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 693, 697 ] ], "normalized": [] }, { "id": "PMID-8663022_T8", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 775, 780 ] ], "normalized": [] }, { "id": "PMID-8663022_T9", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 785, 790 ] ], "normalized": [] }, { "id": "PMID-8663022_T10", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 998, 1001 ] ], "normalized": [] }, { "id": "PMID-8663022_T11", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1053, 1057 ] ], "normalized": [] }, { "id": "PMID-8663022_T12", "type": "Protein", "text": [ "OBF-1" ], "offsets": [ [ 1124, 1129 ] ], "normalized": [] }, { "id": "PMID-8663022_T13", "type": "Protein", "text": [ "Bob1" ], "offsets": [ [ 1130, 1134 ] ], "normalized": [] }, { "id": "PMID-8663022_T14", "type": "Protein", "text": [ "OCA-B" ], "offsets": [ [ 1135, 1140 ] ], "normalized": [] }, { "id": "PMID-8663022_T15", "type": "Protein", "text": [ "OBF-1" ], "offsets": [ [ 1205, 1210 ] ], "normalized": [] }, { "id": "PMID-8663022_T16", "type": "Protein", "text": [ "Bob1" ], "offsets": [ [ 1211, 1215 ] ], "normalized": [] }, { "id": "PMID-8663022_T17", "type": "Protein", "text": [ "OCA-B" ], "offsets": [ [ 1216, 1221 ] ], "normalized": [] }, { "id": "PMID-8663022_T18", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1244, 1248 ] ], "normalized": [] }, { "id": "PMID-8663022_T19", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1377, 1381 ] ], "normalized": [] }, { "id": "PMID-8663022_T20", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 83, 91 ] ], "normalized": [] }, { "id": "PMID-8663022_T21", "type": "Entity", "text": [ "genes" ], "offsets": [ [ 242, 247 ] ], "normalized": [] }, { "id": "PMID-8663022_T22", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 512, 520 ] ], "normalized": [] }, { "id": "PMID-8663022_T23", "type": "Entity", "text": [ "cell type-specific reporter gene" ], "offsets": [ [ 529, 561 ] ], "normalized": [] }, { "id": "PMID-8663022_T24", "type": "Entity", "text": [ "murine PU.1 promoter" ], "offsets": [ [ 686, 706 ] ], "normalized": [] }, { "id": "PMID-8663022_T25", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 698, 706 ] ], "normalized": [] }, { "id": "PMID-8663022_T26", "type": "Entity", "text": [ "site at base pair -55" ], "offsets": [ [ 818, 839 ] ], "normalized": [] }, { "id": "PMID-8663022_T27", "type": "Entity", "text": [ "binding site" ], "offsets": [ [ 1002, 1014 ] ], "normalized": [] }, { "id": "PMID-8663022_T28", "type": "Entity", "text": [ "octamer site" ], "offsets": [ [ 1031, 1043 ] ], "normalized": [] }, { "id": "PMID-8663022_T29", "type": "Entity", "text": [ "autoregulatory site" ], "offsets": [ [ 1058, 1077 ] ], "normalized": [] }, { "id": "PMID-8663022_T30", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1249, 1257 ] ], "normalized": [] }, { "id": "PMID-8663022_T31", "type": "Entity", "text": [ "octamer site" ], "offsets": [ [ 1398, 1410 ] ], "normalized": [] } ]

[]

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[ { "id": "PMID-9136080__text", "type": "abstract", "text": [ "Structure and function analysis of the human myeloid cell nuclear differentiation antigen promoter: evidence for the role of Sp1 and not of c-Myb or PU.1 in myelomonocytic lineage-specific expression. \nThe human myeloid nuclear differentiation antigen (MNDA) is expressed specifically in maturing cells of the myelomonocytic lineage and in monocytes and granulocytes. Epitope enhancement was used to confirm the strict lineage- and stage-specific expression of MNDA in bone marrow as well as in other paraffin-embedded fixed tissues. A 1-kb region of the gene that includes 5' flanking sequence was reported earlier to contain functional promoter activity and was specifically demethylated in expressing cells in contrast to null cells. Further analysis has revealed that this 1-kb fragment promotes higher reporter gene activity in MNDA-expressing cells than non-expressing cells, indicating cell-specific differences in transactivation. This sequence contains consensus elements consistent with myeloid-specific gene expression, including a PU.1 consensus site near the major transcription start site and a cluster of c-Myb sites located several hundred bases upstream of this region. However, analysis of deletion mutants localized nearly all of the promoter activity to a short region (-73 to -16) that did not include the cluster of c-Myb sites. A 4-bp mutation of the core Sp1 consensus element (GC box) (-20) reduced overall promoter activity of the 1-kb fragment. Mutation of the PU.1 site did not significantly affect promoter activity. Only a small region (-35 to +22) including the Sp1 element and transcription start site, but not the PU.1 site was footprinted. The 4-bp mutation of the core Sp1 consensus element abolished footprinting at the site and an antibody super-shift reaction showed that Sp1 is one of the factors binding the consensus site. The Sp1 site also co-localizes with a DNase I hypersensitive site. The results indicate that DNA methylation, chromatin structure, and transactivation at an Sp1 site contribute to the highly restricted expression of this myelomonocytic lineage specific gene.\n" ], "offsets": [ [ 0, 2123 ] ] } ]

[ { "id": "PMID-9136080_T1", "type": "Protein", "text": [ "myeloid cell nuclear differentiation antigen" ], "offsets": [ [ 45, 89 ] ], "normalized": [] }, { "id": "PMID-9136080_T2", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 125, 128 ] ], "normalized": [] }, { "id": "PMID-9136080_T3", "type": "Protein", "text": [ "c-Myb" ], "offsets": [ [ 140, 145 ] ], "normalized": [] }, { "id": "PMID-9136080_T4", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 149, 153 ] ], "normalized": [] }, { "id": "PMID-9136080_T5", "type": "Protein", "text": [ "myeloid nuclear differentiation antigen" ], "offsets": [ [ 212, 251 ] ], "normalized": [] }, { "id": "PMID-9136080_T6", "type": "Protein", "text": [ "MNDA" ], "offsets": [ [ 253, 257 ] ], "normalized": [] }, { "id": "PMID-9136080_T7", "type": "Protein", "text": [ "MNDA" ], "offsets": [ [ 461, 465 ] ], "normalized": [] }, { "id": "PMID-9136080_T8", "type": "Protein", "text": [ "MNDA" ], "offsets": [ [ 833, 837 ] ], "normalized": [] }, { "id": "PMID-9136080_T9", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1043, 1047 ] ], "normalized": [] }, { "id": "PMID-9136080_T10", "type": "Protein", "text": [ "c-Myb" ], "offsets": [ [ 1120, 1125 ] ], "normalized": [] }, { "id": "PMID-9136080_T11", "type": "Protein", "text": [ "c-Myb" ], "offsets": [ [ 1338, 1343 ] ], "normalized": [] }, { "id": "PMID-9136080_T12", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1379, 1382 ] ], "normalized": [] }, { "id": "PMID-9136080_T13", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1488, 1492 ] ], "normalized": [] }, { "id": "PMID-9136080_T14", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1593, 1596 ] ], "normalized": [] }, { "id": "PMID-9136080_T15", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1647, 1651 ] ], "normalized": [] }, { "id": "PMID-9136080_T16", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1704, 1707 ] ], "normalized": [] }, { "id": "PMID-9136080_T17", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1810, 1813 ] ], "normalized": [] }, { "id": "PMID-9136080_T18", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1868, 1871 ] ], "normalized": [] }, { "id": "PMID-9136080_T19", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 2021, 2024 ] ], "normalized": [] }, { "id": "PMID-9136080_T20", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 90, 98 ] ], "normalized": [] }, { "id": "PMID-9136080_T21", "type": "Entity", "text": [ "1-kb region" ], "offsets": [ [ 536, 547 ] ], "normalized": [] }, { "id": "PMID-9136080_T22", "type": "Entity", "text": [ "5' flanking sequence" ], "offsets": [ [ 574, 594 ] ], "normalized": [] }, { "id": "PMID-9136080_T23", "type": "Entity", "text": [ "1-kb fragment" ], "offsets": [ [ 777, 790 ] ], "normalized": [] }, { "id": "PMID-9136080_T24", "type": "Entity", "text": [ "consensus elements" ], "offsets": [ [ 962, 980 ] ], "normalized": [] }, { "id": "PMID-9136080_T25", "type": "Entity", "text": [ "consensus site" ], "offsets": [ [ 1048, 1062 ] ], "normalized": [] }, { "id": "PMID-9136080_T26", "type": "Entity", "text": [ "transcription start site" ], "offsets": [ [ 1078, 1102 ] ], "normalized": [] }, { "id": "PMID-9136080_T27", "type": "Entity", "text": [ "sites" ], "offsets": [ [ 1126, 1131 ] ], "normalized": [] }, { "id": "PMID-9136080_T28", "type": "Entity", "text": [ "deletion mutants" ], "offsets": [ [ 1208, 1224 ] ], "normalized": [] }, { "id": "PMID-9136080_T29", "type": "Entity", "text": [ "-73 to -16" ], "offsets": [ [ 1290, 1300 ] ], "normalized": [] }, { "id": "PMID-9136080_T30", "type": "Entity", "text": [ "sites" ], "offsets": [ [ 1344, 1349 ] ], "normalized": [] }, { "id": "PMID-9136080_T31", "type": "Entity", "text": [ "consensus element" ], "offsets": [ [ 1383, 1400 ] ], "normalized": [] }, { "id": "PMID-9136080_T32", "type": "Entity", "text": [ "GC box" ], "offsets": [ [ 1402, 1408 ] ], "normalized": [] }, { "id": "PMID-9136080_T33", "type": "Entity", "text": [ "1-kb fragment" ], "offsets": [ [ 1457, 1470 ] ], "normalized": [] }, { "id": "PMID-9136080_T34", "type": "Entity", "text": [ "site" ], "offsets": [ [ 1493, 1497 ] ], "normalized": [] }, { "id": "PMID-9136080_T35", "type": "Entity", "text": [ "small region (-35 to +22)" ], "offsets": [ [ 1553, 1578 ] ], "normalized": [] }, { "id": "PMID-9136080_T36", "type": "Entity", "text": [ "element" ], "offsets": [ [ 1597, 1604 ] ], "normalized": [] }, { "id": "PMID-9136080_T37", "type": "Entity", "text": [ "transcription start site" ], "offsets": [ [ 1609, 1633 ] ], "normalized": [] }, { "id": "PMID-9136080_T38", "type": "Entity", "text": [ "site" ], "offsets": [ [ 1652, 1656 ] ], "normalized": [] }, { "id": "PMID-9136080_T39", "type": "Entity", "text": [ "Sp1 consensus element" ], "offsets": [ [ 1704, 1725 ] ], "normalized": [] }, { "id": "PMID-9136080_T40", "type": "Entity", "text": [ "consensus site" ], "offsets": [ [ 1848, 1862 ] ], "normalized": [] }, { "id": "PMID-9136080_T41", "type": "Entity", "text": [ "site" ], "offsets": [ [ 1872, 1876 ] ], "normalized": [] }, { "id": "PMID-9136080_T42", "type": "Entity", "text": [ "DNase I hypersensitive site" ], "offsets": [ [ 1902, 1929 ] ], "normalized": [] }, { "id": "PMID-9136080_T43", "type": "Entity", "text": [ "site" ], "offsets": [ [ 2025, 2029 ] ], "normalized": [] }, { "id": "PMID-9136080_T44", "type": "Entity", "text": [ "myelomonocytic lineage specific gene" ], "offsets": [ [ 2085, 2121 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-9136080_1", "entity_ids": [ "PMID-9136080_T5", "PMID-9136080_T6" ] } ]

[ { "id": "PMID-9136080_R1", "type": "Protein-Component", "arg1_id": "PMID-9136080_T1", "arg2_id": "PMID-9136080_T20", "normalized": [] } ]

[ { "id": "PMID-9416887__text", "type": "abstract", "text": [ "Cyclosporin A inhibits monocyte tissue factor activation in cardiac transplant recipients. \nBACKGROUND: Fibrin deposition and thrombosis have been implicated in both allograft rejection and vasculopathy after cardiac transplantation. Because monocytes play a pivotal role in the pathophysiology of intravascular coagulation activation through their ability to synthesize tissue factor (TF), we asked (1) whether monocyte TF activation occurs in cardiac transplant recipients and (2) whether monocyte TF expression is affected by treatment with cyclosporin A (CsA). METHODS AND RESULTS: We measured levels of TF activity in peripheral blood mononuclear cells and highly purified monocytes/macrophages from 10 consecutive cardiac transplant recipients and 10 healthy control subjects. TF activity generated by both unstimulated and endotoxin-stimulated cells was significantly higher in transplant recipients than in control subjects (P<.05). Increased monocyte TF expression in transplant recipients was shown to be adversely affected by treatment with CsA: TF induction was markedly reduced by CsA serum concentrations reaching peak CsA drug levels. Inhibition of TF induction in the presence of high CsA blood concentrations was also observed when stimulation of cells was performed with interferon-gamma or interleukin-1beta. As shown by reverse transcription-polymerase chain reaction and electrophoretic mobility shift assay, respectively, treatment with CsA leads to decreased TF mRNA expression and reduced activation of the NF-kappaB transcription factor, which is known to contribute to the induction of the TF promotor in human monocytes. CONCLUSIONS: This study demonstrates that TF activation, occurring in mononuclear cells of cardiac transplant recipients, is inhibited by treatment with CsA. Inhibition of monocyte TF induction by CsA may contribute to its successful use in cardiac transplant medicine and might be useful in managing further settings of vascular pathology also known to involve TF expression and NF-kappaB activation.\n" ], "offsets": [ [ 0, 2050 ] ] } ]

[ { "id": "PMID-9416887_T1", "type": "Protein", "text": [ "tissue factor" ], "offsets": [ [ 32, 45 ] ], "normalized": [] }, { "id": "PMID-9416887_T2", "type": "Protein", "text": [ "tissue factor" ], "offsets": [ [ 371, 384 ] ], "normalized": [] }, { "id": "PMID-9416887_T3", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 386, 388 ] ], "normalized": [] }, { "id": "PMID-9416887_T4", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 421, 423 ] ], "normalized": [] }, { "id": "PMID-9416887_T5", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 500, 502 ] ], "normalized": [] }, { "id": "PMID-9416887_T6", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 608, 610 ] ], "normalized": [] }, { "id": "PMID-9416887_T7", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 783, 785 ] ], "normalized": [] }, { "id": "PMID-9416887_T8", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 960, 962 ] ], "normalized": [] }, { "id": "PMID-9416887_T9", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1057, 1059 ] ], "normalized": [] }, { "id": "PMID-9416887_T10", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1164, 1166 ] ], "normalized": [] }, { "id": "PMID-9416887_T11", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 1289, 1305 ] ], "normalized": [] }, { "id": "PMID-9416887_T12", "type": "Protein", "text": [ "interleukin-1beta" ], "offsets": [ [ 1309, 1326 ] ], "normalized": [] }, { "id": "PMID-9416887_T13", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1482, 1484 ] ], "normalized": [] }, { "id": "PMID-9416887_T14", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1616, 1618 ] ], "normalized": [] }, { "id": "PMID-9416887_T15", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1690, 1692 ] ], "normalized": [] }, { "id": "PMID-9416887_T16", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 1829, 1831 ] ], "normalized": [] }, { "id": "PMID-9416887_T17", "type": "Protein", "text": [ "TF" ], "offsets": [ [ 2010, 2012 ] ], "normalized": [] }, { "id": "PMID-9416887_T18", "type": "Entity", "text": [ "Fibrin" ], "offsets": [ [ 104, 110 ] ], "normalized": [] }, { "id": "PMID-9416887_T19", "type": "Entity", "text": [ "NF-kappaB transcription factor" ], "offsets": [ [ 1531, 1561 ] ], "normalized": [] }, { "id": "PMID-9416887_T20", "type": "Entity", "text": [ "promotor" ], "offsets": [ [ 1619, 1627 ] ], "normalized": [] }, { "id": "PMID-9416887_T21", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 2028, 2037 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-9416887_1", "entity_ids": [ "PMID-9416887_T2", "PMID-9416887_T3" ] } ]

[ { "id": "PMID-9416887_R1", "type": "Protein-Component", "arg1_id": "PMID-9416887_T14", "arg2_id": "PMID-9416887_T20", "normalized": [] } ]

[ { "id": "PMID-9018153__text", "type": "abstract", "text": [ "Interaction of transcription factors RFX1 and MIBP1 with the gamma motif of the negative regulatory element of the hepatitis B virus core promoter. \nThe negative regulatory element (NRE) of the hepatitis B virus (HBV) core promoter contains three subregions which act synergistically to suppress core promoter activity. One of these subregions, NRE gamma, is active in both HeLa cervical carcinoma cells and Huh7 hepatoma cells and was found to be bound by a protein factor present in both cell types. Here we show that the transcription factor RFX1 can bind to NRE gamma and transactivate the core promoter through this site. Mutations which abrogated the gene-suppressive activity of NRE gamma prevented RFX1 from binding to NRE gamma. In addition, RFX1 can bind simultaneously, most likely as a heterodimer, with the transcription factor MIBP1 to NRE gamma. In the absence of a cloned MIBP1 gene for further studies, we hypothesize that RFX1 acts with MIBP1 to negatively regulate the core promoter activity through the NRE gamma site. The ability of RFX1 to transactivate the core promoter raises the possibility that RFX1 may play a dual role in regulating HBV gene expression.\n" ], "offsets": [ [ 0, 1183 ] ] } ]

[ { "id": "PMID-9018153_T1", "type": "Protein", "text": [ "RFX1" ], "offsets": [ [ 37, 41 ] ], "normalized": [] }, { "id": "PMID-9018153_T2", "type": "Protein", "text": [ "MIBP1" ], "offsets": [ [ 46, 51 ] ], "normalized": [] }, { "id": "PMID-9018153_T3", "type": "Protein", "text": [ "RFX1" ], "offsets": [ [ 545, 549 ] ], "normalized": [] }, { "id": "PMID-9018153_T4", "type": "Protein", "text": [ "RFX1" ], "offsets": [ [ 706, 710 ] ], "normalized": [] }, { "id": "PMID-9018153_T5", "type": "Protein", "text": [ "RFX1" ], "offsets": [ [ 751, 755 ] ], "normalized": [] }, { "id": "PMID-9018153_T6", "type": "Protein", "text": [ "MIBP1" ], "offsets": [ [ 841, 846 ] ], "normalized": [] }, { "id": "PMID-9018153_T7", "type": "Protein", "text": [ "MIBP1" ], "offsets": [ [ 888, 893 ] ], "normalized": [] }, { "id": "PMID-9018153_T8", "type": "Protein", "text": [ "RFX1" ], "offsets": [ [ 940, 944 ] ], "normalized": [] }, { "id": "PMID-9018153_T9", "type": "Protein", "text": [ "MIBP1" ], "offsets": [ [ 955, 960 ] ], "normalized": [] }, { "id": "PMID-9018153_T10", "type": "Protein", "text": [ "RFX1" ], "offsets": [ [ 1054, 1058 ] ], "normalized": [] }, { "id": "PMID-9018153_T11", "type": "Protein", "text": [ "RFX1" ], "offsets": [ [ 1122, 1126 ] ], "normalized": [] }, { "id": "PMID-9018153_T12", "type": "Entity", "text": [ "gamma motif" ], "offsets": [ [ 61, 72 ] ], "normalized": [] }, { "id": "PMID-9018153_T13", "type": "Entity", "text": [ "negative regulatory element" ], "offsets": [ [ 80, 107 ] ], "normalized": [] }, { "id": "PMID-9018153_T14", "type": "Entity", "text": [ "hepatitis B virus core promoter" ], "offsets": [ [ 115, 146 ] ], "normalized": [] }, { "id": "PMID-9018153_T15", "type": "Entity", "text": [ "negative regulatory element" ], "offsets": [ [ 153, 180 ] ], "normalized": [] }, { "id": "PMID-9018153_T16", "type": "Entity", "text": [ "NRE" ], "offsets": [ [ 182, 185 ] ], "normalized": [] }, { "id": "PMID-9018153_T17", "type": "Entity", "text": [ "hepatitis B virus (HBV) core promoter" ], "offsets": [ [ 194, 231 ] ], "normalized": [] }, { "id": "PMID-9018153_T18", "type": "Entity", "text": [ "subregions" ], "offsets": [ [ 247, 257 ] ], "normalized": [] }, { "id": "PMID-9018153_T19", "type": "Entity", "text": [ "NRE gamma" ], "offsets": [ [ 345, 354 ] ], "normalized": [] }, { "id": "PMID-9018153_T20", "type": "Entity", "text": [ "NRE gamma" ], "offsets": [ [ 562, 571 ] ], "normalized": [] }, { "id": "PMID-9018153_T21", "type": "Entity", "text": [ "core promoter" ], "offsets": [ [ 594, 607 ] ], "normalized": [] }, { "id": "PMID-9018153_T22", "type": "Entity", "text": [ "gene" ], "offsets": [ [ 657, 661 ] ], "normalized": [] }, { "id": "PMID-9018153_T23", "type": "Entity", "text": [ "NRE gamma" ], "offsets": [ [ 686, 695 ] ], "normalized": [] }, { "id": "PMID-9018153_T24", "type": "Entity", "text": [ "NRE gamma" ], "offsets": [ [ 727, 736 ] ], "normalized": [] }, { "id": "PMID-9018153_T25", "type": "Entity", "text": [ "heterodimer" ], "offsets": [ [ 798, 809 ] ], "normalized": [] }, { "id": "PMID-9018153_T26", "type": "Entity", "text": [ "NRE gamma" ], "offsets": [ [ 850, 859 ] ], "normalized": [] }, { "id": "PMID-9018153_T27", "type": "Entity", "text": [ "NRE gamma site" ], "offsets": [ [ 1023, 1037 ] ], "normalized": [] }, { "id": "PMID-9018153_T28", "type": "Entity", "text": [ "core promoter" ], "offsets": [ [ 1080, 1093 ] ], "normalized": [] }, { "id": "PMID-9018153_T29", "type": "Entity", "text": [ "HBV gene" ], "offsets": [ [ 1162, 1170 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-9018153_R1", "type": "Subunit-Complex", "arg1_id": "PMID-9018153_T5", "arg2_id": "PMID-9018153_T25", "normalized": [] }, { "id": "PMID-9018153_R2", "type": "Subunit-Complex", "arg1_id": "PMID-9018153_T6", "arg2_id": "PMID-9018153_T25", "normalized": [] } ]

[ { "id": "PMID-9119025__text", "type": "abstract", "text": [ "Cell-to-cell contact activates the long terminal repeat of human immunodeficiency virus 1 through its kappaB motif. \nCell-to-cell contact between peripheral blood lymphocytes and transfected human colonic carcinoma cell line HT29 activates transcription of the long terminal repeats (LTR) of human immunodeficiency virus. HIV-1 LTR transcription is controlled by a complex array of virus-encoded and cellular proteins. Using various constructs expressing a lacZ reporter gene under the control of the intact or three deleted forms of HIV-1 LTR, we obtained evidence that the kappaB regulatory elements located in the U3 region are involved in cell-to-cell activation of HIV-1 LTR. Cell-to-cell contact activates in vitro binding of the nuclear factor kappaB (NF-kappaB) p50/p65 heterodimer to an HIV-1 kappaB oligonucleotide. Cell-to-cell contact activation of NF-kappaB was only partially inhibited by 100 microM pyrrolidine dithiocarbamate and was not correlated with a significant decrease of cellular inhibitor kappaB alpha. NF-kappaB nuclear activation was not detectable before 1 h after cell contact and was dependent on protein synthesis.\n" ], "offsets": [ [ 0, 1147 ] ] } ]

[ { "id": "PMID-9119025_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 770, 773 ] ], "normalized": [] }, { "id": "PMID-9119025_T2", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 774, 777 ] ], "normalized": [] }, { "id": "PMID-9119025_T3", "type": "Protein", "text": [ "inhibitor kappaB alpha" ], "offsets": [ [ 1005, 1027 ] ], "normalized": [] }, { "id": "PMID-9119025_T4", "type": "Entity", "text": [ "long terminal repeat" ], "offsets": [ [ 35, 55 ] ], "normalized": [] }, { "id": "PMID-9119025_T5", "type": "Entity", "text": [ "kappaB motif" ], "offsets": [ [ 102, 114 ] ], "normalized": [] }, { "id": "PMID-9119025_T6", "type": "Entity", "text": [ "long terminal repeats" ], "offsets": [ [ 261, 282 ] ], "normalized": [] }, { "id": "PMID-9119025_T7", "type": "Entity", "text": [ "LTR" ], "offsets": [ [ 284, 287 ] ], "normalized": [] }, { "id": "PMID-9119025_T8", "type": "Entity", "text": [ "HIV-1 LTR" ], "offsets": [ [ 322, 331 ] ], "normalized": [] }, { "id": "PMID-9119025_T9", "type": "Entity", "text": [ "lacZ reporter gene" ], "offsets": [ [ 457, 475 ] ], "normalized": [] }, { "id": "PMID-9119025_T10", "type": "Entity", "text": [ "HIV-1 LTR" ], "offsets": [ [ 534, 543 ] ], "normalized": [] }, { "id": "PMID-9119025_T11", "type": "Entity", "text": [ "kappaB regulatory elements" ], "offsets": [ [ 575, 601 ] ], "normalized": [] }, { "id": "PMID-9119025_T12", "type": "Entity", "text": [ "U3 region" ], "offsets": [ [ 617, 626 ] ], "normalized": [] }, { "id": "PMID-9119025_T13", "type": "Entity", "text": [ "HIV-1 LTR" ], "offsets": [ [ 670, 679 ] ], "normalized": [] }, { "id": "PMID-9119025_T14", "type": "Entity", "text": [ "heterodimer" ], "offsets": [ [ 778, 789 ] ], "normalized": [] }, { "id": "PMID-9119025_T15", "type": "Entity", "text": [ "HIV-1 kappaB oligonucleotide" ], "offsets": [ [ 796, 824 ] ], "normalized": [] }, { "id": "PMID-9119025_T16", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 861, 870 ] ], "normalized": [] }, { "id": "PMID-9119025_T17", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1029, 1038 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-9119025_R1", "type": "Subunit-Complex", "arg1_id": "PMID-9119025_T1", "arg2_id": "PMID-9119025_T14", "normalized": [] }, { "id": "PMID-9119025_R2", "type": "Subunit-Complex", "arg1_id": "PMID-9119025_T2", "arg2_id": "PMID-9119025_T14", "normalized": [] } ]

[ { "id": "PMID-7859743__text", "type": "abstract", "text": [ "HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state. \nThis study demonstrates that human immunodeficiency virus type 1 (HIV-1) Tat protein amplifies the activity of tumor necrosis factor (TNF), a cytokine that stimulates HIV-1 replication through activation of NF-kappa B. In HeLa cells stably transfected with the HIV-1 tat gene (HeLa-tat cells), expression of the Tat protein enhanced both TNF-induced activation of NF-kappa B and TNF-mediated cytotoxicity. A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein. TNF-mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates. Therefore, Tat-mediated effects on the cellular redox state were analyzed. In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase (Mn-SOD), a mitochondrial enzyme that is part of the cellular defense system against oxidative stress. Thus, Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat. Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced:oxidized glutathione. A truncated Tat protein (Tat1-72), known to transactivate the HIV-1 long terminal repeat (LTR), no longer affected Mn-SOD expression, the cellular redox state or TNF-mediated cytotoxicity. Thus, our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione (GSH) and the GSH:oxidized GSH (GSSG) ratio. (ABSTRACT TRUNCATED AT 250 WORDS)\n" ], "offsets": [ [ 0, 1732 ] ] } ]

[ { "id": "PMID-7859743_T1", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 6, 9 ] ], "normalized": [] }, { "id": "PMID-7859743_T2", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 185, 188 ] ], "normalized": [] }, { "id": "PMID-7859743_T3", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 424, 427 ] ], "normalized": [] }, { "id": "PMID-7859743_T4", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 623, 626 ] ], "normalized": [] }, { "id": "PMID-7859743_T5", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 773, 776 ] ], "normalized": [] }, { "id": "PMID-7859743_T6", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 874, 877 ] ], "normalized": [] }, { "id": "PMID-7859743_T7", "type": "Protein", "text": [ "Mn-dependent superoxide dismutase" ], "offsets": [ [ 907, 940 ] ], "normalized": [] }, { "id": "PMID-7859743_T8", "type": "Protein", "text": [ "Mn-SOD" ], "offsets": [ [ 942, 948 ] ], "normalized": [] }, { "id": "PMID-7859743_T9", "type": "Protein", "text": [ "Mn-SOD" ], "offsets": [ [ 1050, 1056 ] ], "normalized": [] }, { "id": "PMID-7859743_T10", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1130, 1133 ] ], "normalized": [] }, { "id": "PMID-7859743_T11", "type": "Protein", "text": [ "Mn-SOD" ], "offsets": [ [ 1145, 1151 ] ], "normalized": [] }, { "id": "PMID-7859743_T12", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1278, 1281 ] ], "normalized": [] }, { "id": "PMID-7859743_T13", "type": "Protein", "text": [ "Mn-SOD" ], "offsets": [ [ 1381, 1387 ] ], "normalized": [] }, { "id": "PMID-7859743_T14", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1525, 1528 ] ], "normalized": [] }, { "id": "PMID-7859743_T15", "type": "Protein", "text": [ "Mn-SOD" ], "offsets": [ [ 1553, 1559 ] ], "normalized": [] }, { "id": "PMID-7859743_T16", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 34, 44 ] ], "normalized": [] }, { "id": "PMID-7859743_T17", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 319, 329 ] ], "normalized": [] }, { "id": "PMID-7859743_T18", "type": "Entity", "text": [ "HIV-1 tat gene" ], "offsets": [ [ 373, 387 ] ], "normalized": [] }, { "id": "PMID-7859743_T19", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 476, 486 ] ], "normalized": [] }, { "id": "PMID-7859743_T20", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 663, 673 ] ], "normalized": [] }, { "id": "PMID-7859743_T21", "type": "Entity", "text": [ "glutathione" ], "offsets": [ [ 1203, 1214 ] ], "normalized": [] }, { "id": "PMID-7859743_T22", "type": "Entity", "text": [ "glutathione" ], "offsets": [ [ 1253, 1264 ] ], "normalized": [] }, { "id": "PMID-7859743_T23", "type": "Entity", "text": [ "HIV-1 long terminal repeat" ], "offsets": [ [ 1328, 1354 ] ], "normalized": [] }, { "id": "PMID-7859743_T24", "type": "Entity", "text": [ "LTR" ], "offsets": [ [ 1356, 1359 ] ], "normalized": [] }, { "id": "PMID-7859743_T25", "type": "Entity", "text": [ "C-terminal region of HIV-1 Tat" ], "offsets": [ [ 1498, 1528 ] ], "normalized": [] }, { "id": "PMID-7859743_T26", "type": "Entity", "text": [ "C-terminal region" ], "offsets": [ [ 1498, 1515 ] ], "normalized": [] }, { "id": "PMID-7859743_T27", "type": "Entity", "text": [ "glutathione" ], "offsets": [ [ 1641, 1652 ] ], "normalized": [] }, { "id": "PMID-7859743_T28", "type": "Entity", "text": [ "GSH" ], "offsets": [ [ 1654, 1657 ] ], "normalized": [] }, { "id": "PMID-7859743_T29", "type": "Entity", "text": [ "GSH" ], "offsets": [ [ 1680, 1683 ] ], "normalized": [] }, { "id": "PMID-7859743_T30", "type": "Entity", "text": [ "GSSG" ], "offsets": [ [ 1685, 1689 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-7859743_1", "entity_ids": [ "PMID-7859743_T7", "PMID-7859743_T8" ] } ]

[ { "id": "PMID-7859743_R1", "type": "Protein-Component", "arg1_id": "PMID-7859743_T14", "arg2_id": "PMID-7859743_T25", "normalized": [] } ]

[ { "id": "PMID-10233927__text", "type": "abstract", "text": [ "Control of cell cycle entry and apoptosis in B lymphocytes infected by Epstein-Barr virus. \nInfection of human B cells with Epstein-Barr virus (EBV) results in activation of the cell cycle and cell growth. To interpret the mechanisms by which EBV activates the cell, we have assayed many proteins involved in control of the G0 and G1 phases of the cell cycle and regulation of apoptosis. In EBV infection most of the changes, including the early induction of cyclin D2, are dependent on expression of EBV genes, but an alteration in the E2F-4 profile was partly independent of viral gene expression, presumably occurring in response to signal transduction activated when the virus binds to its receptor, CD21. By comparing the expression of genes controlling apoptosis, including those encoding several members of the BCL-2 family of proteins, the known relative resistance of EBV-immortalized B-cell lines to apoptosis induced by low serum was found to correlate with expression of both BCL-2 and A20. A20 can be regulated by the NF-kappaB transcription factor, which is known to be activated by the EBV LMP-1 protein. Quantitative assays demonstrated a direct temporal relationship between LMP-1 protein levels and active NF-kappaB during the time course of infection.\n" ], "offsets": [ [ 0, 1271 ] ] } ]

[ { "id": "PMID-10233927_T1", "type": "Protein", "text": [ "cyclin D2" ], "offsets": [ [ 459, 468 ] ], "normalized": [] }, { "id": "PMID-10233927_T2", "type": "Protein", "text": [ "E2F-4" ], "offsets": [ [ 537, 542 ] ], "normalized": [] }, { "id": "PMID-10233927_T3", "type": "Protein", "text": [ "CD21" ], "offsets": [ [ 704, 708 ] ], "normalized": [] }, { "id": "PMID-10233927_T4", "type": "Protein", "text": [ "BCL-2" ], "offsets": [ [ 988, 993 ] ], "normalized": [] }, { "id": "PMID-10233927_T5", "type": "Protein", "text": [ "A20" ], "offsets": [ [ 998, 1001 ] ], "normalized": [] }, { "id": "PMID-10233927_T6", "type": "Protein", "text": [ "A20" ], "offsets": [ [ 1003, 1006 ] ], "normalized": [] }, { "id": "PMID-10233927_T7", "type": "Protein", "text": [ "LMP-1" ], "offsets": [ [ 1105, 1110 ] ], "normalized": [] }, { "id": "PMID-10233927_T8", "type": "Protein", "text": [ "LMP-1" ], "offsets": [ [ 1192, 1197 ] ], "normalized": [] }, { "id": "PMID-10233927_T9", "type": "Entity", "text": [ "EBV genes" ], "offsets": [ [ 501, 510 ] ], "normalized": [] }, { "id": "PMID-10233927_T10", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1031, 1040 ] ], "normalized": [] }, { "id": "PMID-10233927_T11", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1224, 1233 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-7659529__text", "type": "abstract", "text": [ "Regulation of transcription of the human erythropoietin receptor gene by proteins binding to GATA-1 and Sp1 motifs. \nErythropoietin (Epo), the primary regulator of the production of erythroid cells, acts by binding to a cell surface receptor (EpoR) on erythroid progenitors. We used deletion analysis and transfection assays with reporter gene constructs to examine the transcription control elements in the 5' flanking region of the human EpoR gene. In erythroid cells most of the transcription activity was contained in a 150 bp promoter fragment with binding sites for transcription factors AP2, Sp1 and the erythroid-specific GATA-1. The 150 bp hEpoR promoter exhibited high and low activity in erythroid OCIM1 and K562 cells, respectively, reflecting the high and low levels of constitutive hEpoR expression. The GATA-1 and Sp1 binding sites in this promoter lacking a TATA sequence were necessary for a high level of transcription activation. Protein-DNA binding studies suggested that Sp1 and two other CCGCCC binding proteins from erythroid and non-erythroid cells could bind to the Sp1 binding motif. By increasing GATA-1 levels via co-transfection, we were able to transactivate the hEpoR promoter in K562 cells and non-erythroid cells, but not in the highly active OCIM1 cells, although GATA-1 mRNA levels were comparable in OCIM1 and K562. Interestingly, when we mutated the Sp1 site, resulting in a marked decrease in hEpoR promoter activity, we could restore transactivation by increasing GATA-1 levels in OCIM1 cells. These data suggest that while GATA-1 can transactivate the EpoR promoter, the level of hEpoR gene expression does not depend on GATA-1 alone. Rather, hEpoR transcription activity depends on coordination between Sp1 and GATA-1 with other cell-specific factors, including possibly other Sp1-like binding proteins, to provide high level, tissue-specific expression.\n" ], "offsets": [ [ 0, 1896 ] ] } ]

[ { "id": "PMID-7659529_T1", "type": "Protein", "text": [ "erythropoietin receptor" ], "offsets": [ [ 41, 64 ] ], "normalized": [] }, { "id": "PMID-7659529_T2", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 93, 99 ] ], "normalized": [] }, { "id": "PMID-7659529_T3", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 104, 107 ] ], "normalized": [] }, { "id": "PMID-7659529_T4", "type": "Protein", "text": [ "Erythropoietin" ], "offsets": [ [ 117, 131 ] ], "normalized": [] }, { "id": "PMID-7659529_T5", "type": "Protein", "text": [ "Epo" ], "offsets": [ [ 133, 136 ] ], "normalized": [] }, { "id": "PMID-7659529_T6", "type": "Protein", "text": [ "EpoR" ], "offsets": [ [ 243, 247 ] ], "normalized": [] }, { "id": "PMID-7659529_T7", "type": "Protein", "text": [ "EpoR" ], "offsets": [ [ 440, 444 ] ], "normalized": [] }, { "id": "PMID-7659529_T8", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 599, 602 ] ], "normalized": [] }, { "id": "PMID-7659529_T9", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 630, 636 ] ], "normalized": [] }, { "id": "PMID-7659529_T10", "type": "Protein", "text": [ "hEpoR" ], "offsets": [ [ 649, 654 ] ], "normalized": [] }, { "id": "PMID-7659529_T11", "type": "Protein", "text": [ "hEpoR" ], "offsets": [ [ 796, 801 ] ], "normalized": [] }, { "id": "PMID-7659529_T12", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 818, 824 ] ], "normalized": [] }, { "id": "PMID-7659529_T13", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 829, 832 ] ], "normalized": [] }, { "id": "PMID-7659529_T14", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 992, 995 ] ], "normalized": [] }, { "id": "PMID-7659529_T15", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1091, 1094 ] ], "normalized": [] }, { "id": "PMID-7659529_T16", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1124, 1130 ] ], "normalized": [] }, { "id": "PMID-7659529_T17", "type": "Protein", "text": [ "hEpoR" ], "offsets": [ [ 1193, 1198 ] ], "normalized": [] }, { "id": "PMID-7659529_T18", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1298, 1304 ] ], "normalized": [] }, { "id": "PMID-7659529_T19", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1387, 1390 ] ], "normalized": [] }, { "id": "PMID-7659529_T20", "type": "Protein", "text": [ "hEpoR" ], "offsets": [ [ 1431, 1436 ] ], "normalized": [] }, { "id": "PMID-7659529_T21", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1503, 1509 ] ], "normalized": [] }, { "id": "PMID-7659529_T22", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1563, 1569 ] ], "normalized": [] }, { "id": "PMID-7659529_T23", "type": "Protein", "text": [ "EpoR" ], "offsets": [ [ 1592, 1596 ] ], "normalized": [] }, { "id": "PMID-7659529_T24", "type": "Protein", "text": [ "hEpoR" ], "offsets": [ [ 1620, 1625 ] ], "normalized": [] }, { "id": "PMID-7659529_T25", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1661, 1667 ] ], "normalized": [] }, { "id": "PMID-7659529_T26", "type": "Protein", "text": [ "hEpoR" ], "offsets": [ [ 1683, 1688 ] ], "normalized": [] }, { "id": "PMID-7659529_T27", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1744, 1747 ] ], "normalized": [] }, { "id": "PMID-7659529_T28", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1752, 1758 ] ], "normalized": [] }, { "id": "PMID-7659529_T29", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1818, 1821 ] ], "normalized": [] }, { "id": "PMID-7659529_T30", "type": "Entity", "text": [ "motifs" ], "offsets": [ [ 108, 114 ] ], "normalized": [] }, { "id": "PMID-7659529_T31", "type": "Entity", "text": [ "transcription control elements" ], "offsets": [ [ 370, 400 ] ], "normalized": [] }, { "id": "PMID-7659529_T32", "type": "Entity", "text": [ "5' flanking region" ], "offsets": [ [ 408, 426 ] ], "normalized": [] }, { "id": "PMID-7659529_T33", "type": "Entity", "text": [ "150 bp promoter fragment" ], "offsets": [ [ 524, 548 ] ], "normalized": [] }, { "id": "PMID-7659529_T34", "type": "Entity", "text": [ "binding sites" ], "offsets": [ [ 554, 567 ] ], "normalized": [] }, { "id": "PMID-7659529_T35", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 655, 663 ] ], "normalized": [] }, { "id": "PMID-7659529_T36", "type": "Entity", "text": [ "binding sites" ], "offsets": [ [ 833, 846 ] ], "normalized": [] }, { "id": "PMID-7659529_T37", "type": "Entity", "text": [ "TATA sequence" ], "offsets": [ [ 874, 887 ] ], "normalized": [] }, { "id": "PMID-7659529_T38", "type": "Entity", "text": [ "binding motif" ], "offsets": [ [ 1095, 1108 ] ], "normalized": [] }, { "id": "PMID-7659529_T39", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1199, 1207 ] ], "normalized": [] }, { "id": "PMID-7659529_T40", "type": "Entity", "text": [ "site" ], "offsets": [ [ 1391, 1395 ] ], "normalized": [] }, { "id": "PMID-7659529_T41", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1437, 1445 ] ], "normalized": [] }, { "id": "PMID-7659529_T42", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1597, 1605 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-7659529_1", "entity_ids": [ "PMID-7659529_T4", "PMID-7659529_T5" ] } ]

[ { "id": "PMID-7659529_R1", "type": "Protein-Component", "arg1_id": "PMID-7659529_T2", "arg2_id": "PMID-7659529_T30", "normalized": [] }, { "id": "PMID-7659529_R2", "type": "Protein-Component", "arg1_id": "PMID-7659529_T3", "arg2_id": "PMID-7659529_T30", "normalized": [] }, { "id": "PMID-7659529_R3", "type": "Protein-Component", "arg1_id": "PMID-7659529_T7", "arg2_id": "PMID-7659529_T31", "normalized": [] }, { "id": "PMID-7659529_R4", "type": "Protein-Component", "arg1_id": "PMID-7659529_T7", "arg2_id": "PMID-7659529_T32", "normalized": [] }, { "id": "PMID-7659529_R5", "type": "Protein-Component", "arg1_id": "PMID-7659529_T10", "arg2_id": "PMID-7659529_T35", "normalized": [] }, { "id": "PMID-7659529_R6", "type": "Protein-Component", "arg1_id": "PMID-7659529_T17", "arg2_id": "PMID-7659529_T39", "normalized": [] }, { "id": "PMID-7659529_R7", "type": "Protein-Component", "arg1_id": "PMID-7659529_T20", "arg2_id": "PMID-7659529_T40", "normalized": [] }, { "id": "PMID-7659529_R8", "type": "Protein-Component", "arg1_id": "PMID-7659529_T20", "arg2_id": "PMID-7659529_T41", "normalized": [] }, { "id": "PMID-7659529_R9", "type": "Protein-Component", "arg1_id": "PMID-7659529_T23", "arg2_id": "PMID-7659529_T42", "normalized": [] } ]

[ { "id": "PMID-8179594__text", "type": "abstract", "text": [ "Effects of alpha-lipoic acid and dihydrolipoic acid on expression of proto-oncogene c-fos. \nThe transcription factor AP-1 is an important human mediator of the cellular response to serum, growth factors, and phorbol esters such as 12-O-tetradecanoyl-phorbol-13 acetate (TPA). The AP-1 complex consists of distinct protein heterodimers encoded by the proto-oncogene c-fos and c-jun mRNA whose gene expression can be induced by TPA, cyclic AMP and growth factors. Recent findings suggest an involvement of reactive oxygen species in the pathway of TPA and protein kinase C leading to expression of c-fos and c-jun mRNA. To investigate the role of reactive oxygen species we studied the effects of alpha-lipoic acid and dihydrolipoic acid (natural thiol antioxidants) on the expression of c-fos mRNA in human Jurkat T cells. When cells were preincubated with dihydrolipoic acid (0.2 mM) the expression of c-fos mRNA was suppressed at 30 min after stimulation of TPA (0.5 microM) whereas in the case of preincubation of alpha-lipoic acid (0.2 microM), the expression was enhanced at 30 min. These studies support the idea that superoxide anion radical plays a role in the expression of c-fos mRNA.\n" ], "offsets": [ [ 0, 1194 ] ] } ]

[ { "id": "PMID-8179594_T1", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 84, 89 ] ], "normalized": [] }, { "id": "PMID-8179594_T2", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 365, 370 ] ], "normalized": [] }, { "id": "PMID-8179594_T3", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 375, 380 ] ], "normalized": [] }, { "id": "PMID-8179594_T4", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 596, 601 ] ], "normalized": [] }, { "id": "PMID-8179594_T5", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 606, 611 ] ], "normalized": [] }, { "id": "PMID-8179594_T6", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 786, 791 ] ], "normalized": [] }, { "id": "PMID-8179594_T7", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 902, 907 ] ], "normalized": [] }, { "id": "PMID-8179594_T8", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1182, 1187 ] ], "normalized": [] }, { "id": "PMID-8179594_T9", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 117, 121 ] ], "normalized": [] }, { "id": "PMID-8179594_T10", "type": "Entity", "text": [ "AP-1 complex" ], "offsets": [ [ 280, 292 ] ], "normalized": [] }, { "id": "PMID-8179594_T11", "type": "Entity", "text": [ "protein heterodimers" ], "offsets": [ [ 314, 334 ] ], "normalized": [] }, { "id": "PMID-8179594_T12", "type": "Entity", "text": [ "cyclic AMP" ], "offsets": [ [ 431, 441 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-8179594_R1", "type": "Subunit-Complex", "arg1_id": "PMID-8179594_T3", "arg2_id": "PMID-8179594_T11", "normalized": [] }, { "id": "PMID-8179594_R2", "type": "Subunit-Complex", "arg1_id": "PMID-8179594_T2", "arg2_id": "PMID-8179594_T11", "normalized": [] }, { "id": "PMID-8179594_R3", "type": "Subunit-Complex", "arg1_id": "PMID-8179594_T2", "arg2_id": "PMID-8179594_T10", "normalized": [] }, { "id": "PMID-8179594_R4", "type": "Subunit-Complex", "arg1_id": "PMID-8179594_T3", "arg2_id": "PMID-8179594_T10", "normalized": [] } ]

[ { "id": "PMID-8562886__text", "type": "abstract", "text": [ "The effect of Toremifene on the expression of some genes in human mononuclear cells. \nToremifene exerts multiple and varied effects on the gene expression of human peripheral mononuclear cells. After short-term, in vitro exposure to therapeutical levels, distinct changes in P-glycoprotein, steroid receptors, p53 and Bcl-2 expression take place. In view of the increasing use of antiestrogens in cancer therapy and prevention, there is obvious merit in long-term in vivo studies to be conducted.\n" ], "offsets": [ [ 0, 497 ] ] } ]

[ { "id": "PMID-8562886_T1", "type": "Protein", "text": [ "p53" ], "offsets": [ [ 310, 313 ] ], "normalized": [] }, { "id": "PMID-8562886_T2", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 318, 323 ] ], "normalized": [] }, { "id": "PMID-8562886_T3", "type": "Entity", "text": [ "genes" ], "offsets": [ [ 51, 56 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-8725939__text", "type": "abstract", "text": [ "Regulation of gene expression at early stages of B-cell and T-cell differentiation. \nThe expression of distinct sets of genes at different stages of B-lymphocyte and T-lymphocyte differentiation is controlled at the level of transcription. A number of recent studies have described interactions between transcription factors in lymphocytes that provide new insights into mechanisms regulating gene expression. These mechanisms include the assembly of higher order nucleoprotein complexes and other protein-protein interactions that enhance the functional specificity of transcriptional regulators in lymphocytes.\n" ], "offsets": [ [ 0, 613 ] ] } ]

[ { "id": "PMID-8725939_T1", "type": "Entity", "text": [ "genes" ], "offsets": [ [ 120, 125 ] ], "normalized": [] }, { "id": "PMID-8725939_T2", "type": "Entity", "text": [ "higher order nucleoprotein complexes" ], "offsets": [ [ 451, 487 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-8577772__text", "type": "abstract", "text": [ "In vivo anergized CD4+ T cells express perturbed AP-1 and NF-kappa B transcription factors. \nAnergy is a major mechanism to ensure antigen-specific tolerance in T lymphocytes in the adult. In vivo, anergy has mainly been studied at the cellular level. In this study, we used the T-cell-activating superantigen staphylococcal enterotoxin A (SEA) to investigate molecular mechanisms of T-lymphocyte anergy in vivo. Injection of SEA to adult mice activates CD4+ T cells expressing certain T-cell receptor (TCR) variable region beta-chain families and induces strong and rapid production of interleukin 2 (IL-2). In contrast, repeated injections of SEA cause CD4+ T-cell deletion and anergy in the remaining CD4+ T cells, characterized by reduced expression of IL-2 at mRNA and protein levels. We analyzed expression of AP-1, NF-kappa B, NF-AT, and octamer binding transcription factors, which are known to be involved in the regulation of IL-2 gene promoter activity. Large amounts of AP-1 and NF-kappa B and significant quantities of NF-AT were induced in SEA-activated CD4+ spleen T cells, whereas Oct-1 and Oct-2 DNA binding activity was similar in both resting and activated T cells. In contrast, anergic CD4+ T cells contained severely reduced levels of AP-1 and Fos/Jun-containing NF-AT complexes but expressed significant amounts of NF-kappa B and Oct binding proteins after SEA stimulation. Resolution of the NF-kappa B complex demonstrated predominant expression of p50-p65 heterodimers in activated CD4+ T cells, while anergic cells mainly expressed the transcriptionally inactive p50 homodimer. These alterations of transcription factors are likely to be responsible for repression of IL-2 in anergic T cells.\n" ], "offsets": [ [ 0, 1718 ] ] } ]

[ { "id": "PMID-8577772_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 18, 21 ] ], "normalized": [] }, { "id": "PMID-8577772_T2", "type": "Protein", "text": [ "staphylococcal enterotoxin A" ], "offsets": [ [ 310, 338 ] ], "normalized": [] }, { "id": "PMID-8577772_T3", "type": "Protein", "text": [ "SEA" ], "offsets": [ [ 340, 343 ] ], "normalized": [] }, { "id": "PMID-8577772_T4", "type": "Protein", "text": [ "SEA" ], "offsets": [ [ 426, 429 ] ], "normalized": [] }, { "id": "PMID-8577772_T5", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 454, 457 ] ], "normalized": [] }, { "id": "PMID-8577772_T6", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 587, 600 ] ], "normalized": [] }, { "id": "PMID-8577772_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 602, 606 ] ], "normalized": [] }, { "id": "PMID-8577772_T8", "type": "Protein", "text": [ "SEA" ], "offsets": [ [ 645, 648 ] ], "normalized": [] }, { "id": "PMID-8577772_T9", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 655, 658 ] ], "normalized": [] }, { "id": "PMID-8577772_T10", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 704, 707 ] ], "normalized": [] }, { "id": "PMID-8577772_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 757, 761 ] ], "normalized": [] }, { "id": "PMID-8577772_T12", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 936, 940 ] ], "normalized": [] }, { "id": "PMID-8577772_T13", "type": "Protein", "text": [ "SEA" ], "offsets": [ [ 1054, 1057 ] ], "normalized": [] }, { "id": "PMID-8577772_T14", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1068, 1071 ] ], "normalized": [] }, { "id": "PMID-8577772_T15", "type": "Protein", "text": [ "Oct-1" ], "offsets": [ [ 1097, 1102 ] ], "normalized": [] }, { "id": "PMID-8577772_T16", "type": "Protein", "text": [ "Oct-2" ], "offsets": [ [ 1107, 1112 ] ], "normalized": [] }, { "id": "PMID-8577772_T17", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1206, 1209 ] ], "normalized": [] }, { "id": "PMID-8577772_T18", "type": "Protein", "text": [ "Fos" ], "offsets": [ [ 1265, 1268 ] ], "normalized": [] }, { "id": "PMID-8577772_T19", "type": "Protein", "text": [ "Jun" ], "offsets": [ [ 1269, 1272 ] ], "normalized": [] }, { "id": "PMID-8577772_T20", "type": "Protein", "text": [ "SEA" ], "offsets": [ [ 1379, 1382 ] ], "normalized": [] }, { "id": "PMID-8577772_T21", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1472, 1475 ] ], "normalized": [] }, { "id": "PMID-8577772_T22", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1476, 1479 ] ], "normalized": [] }, { "id": "PMID-8577772_T23", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 1506, 1509 ] ], "normalized": [] }, { "id": "PMID-8577772_T24", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1588, 1591 ] ], "normalized": [] }, { "id": "PMID-8577772_T25", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1693, 1697 ] ], "normalized": [] }, { "id": "PMID-8577772_T26", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 946, 954 ] ], "normalized": [] }, { "id": "PMID-8577772_T27", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 1256, 1260 ] ], "normalized": [] }, { "id": "PMID-8577772_T28", "type": "Entity", "text": [ "-containing NF-AT complexes" ], "offsets": [ [ 1272, 1299 ] ], "normalized": [] }, { "id": "PMID-8577772_T29", "type": "Entity", "text": [ "NF-kappa B complex" ], "offsets": [ [ 1414, 1432 ] ], "normalized": [] }, { "id": "PMID-8577772_T30", "type": "Entity", "text": [ "heterodimers" ], "offsets": [ [ 1480, 1492 ] ], "normalized": [] }, { "id": "PMID-8577772_T31", "type": "Entity", "text": [ "homodimer" ], "offsets": [ [ 1592, 1601 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-8577772_1", "entity_ids": [ "PMID-8577772_T2", "PMID-8577772_T3" ] }, { "id": "PMID-8577772_2", "entity_ids": [ "PMID-8577772_T6", "PMID-8577772_T7" ] } ]

[ { "id": "PMID-8577772_R1", "type": "Protein-Component", "arg1_id": "PMID-8577772_T12", "arg2_id": "PMID-8577772_T26", "normalized": [] }, { "id": "PMID-8577772_R2", "type": "Subunit-Complex", "arg1_id": "PMID-8577772_T18", "arg2_id": "PMID-8577772_T28", "normalized": [] }, { "id": "PMID-8577772_R3", "type": "Subunit-Complex", "arg1_id": "PMID-8577772_T19", "arg2_id": "PMID-8577772_T28", "normalized": [] }, { "id": "PMID-8577772_R4", "type": "Subunit-Complex", "arg1_id": "PMID-8577772_T21", "arg2_id": "PMID-8577772_T29", "normalized": [] }, { "id": "PMID-8577772_R5", "type": "Subunit-Complex", "arg1_id": "PMID-8577772_T24", "arg2_id": "PMID-8577772_T29", "normalized": [] }, { "id": "PMID-8577772_R6", "type": "Subunit-Complex", "arg1_id": "PMID-8577772_T22", "arg2_id": "PMID-8577772_T29", "normalized": [] }, { "id": "PMID-8577772_R7", "type": "Subunit-Complex", "arg1_id": "PMID-8577772_T21", "arg2_id": "PMID-8577772_T30", "normalized": [] }, { "id": "PMID-8577772_R8", "type": "Subunit-Complex", "arg1_id": "PMID-8577772_T22", "arg2_id": "PMID-8577772_T30", "normalized": [] }, { "id": "PMID-8577772_R9", "type": "Subunit-Complex", "arg1_id": "PMID-8577772_T24", "arg2_id": "PMID-8577772_T31", "normalized": [] } ]

[ { "id": "PMID-1645452__text", "type": "abstract", "text": [ "The human myelomonocytic cell line U-937 as a model for studying alterations in steroid-induced monokine gene expression: marked enhancement of lipopolysaccharide-stimulated interleukin-1 beta messenger RNA levels by 1,25-dihydroxyvitamin D3. \nThe active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], is a potent regulator of human monocyte/macrophage function in vitro. To establish a model for 1,25-(OH)2D3 regulation of human monocyte monokine synthesis, three human cell lines (U-937, THP-1, and HL-60) were examined for: 1) the presence of functional 1,25-(OH)2D3 receptors; 2) the accumulation of interleukin-1 beta (IL-1 beta) mRNA and IL-1 beta protein in response to lipopolysaccharide (LPS); and 3) the regulation of this response by 1,25-(OH)2D3. All three cell lines expressed vitamin D receptor and had increased levels of IL-1 beta mRNA in response to LPS. Preincubation of cells with 1,25-(OH)2D3 augmented IL-1 beta mRNA levels only in U-937 and HL-60 cells. From these data, and taking into consideration their state of differentiation and relative ease of culture, U-937 was chosen over HL-60 and THP-1 as the cell line we further characterized. In U-937 cells, optimum time and dose of pretreatment with 1,25-(OH)2D3 were determined to be 12-24 h at a receptor saturating concentration of 1,25-(OH)2D3 (10 nM). Preincubation of cells with 1,25-(OH)2D3 had no effect on the time course of IL-1 beta mRNA appearance in response to LPS. However, exposure of U-937 cells to 1,25-(OH)2D3 increased by 200% the level of IL-1 beta mRNA detected and decreased by three orders of magnitude the concentration of LPS required to achieve steady state mRNA levels equivalent to those observed in U-937 cells not preincubated with the hormone.2+o\n" ], "offsets": [ [ 0, 1772 ] ] } ]

[ { "id": "PMID-1645452_T1", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 174, 192 ] ], "normalized": [] }, { "id": "PMID-1645452_T2", "type": "Protein", "text": [ "interleukin-1 beta" ], "offsets": [ [ 623, 641 ] ], "normalized": [] }, { "id": "PMID-1645452_T3", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 643, 652 ] ], "normalized": [] }, { "id": "PMID-1645452_T4", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 663, 672 ] ], "normalized": [] }, { "id": "PMID-1645452_T5", "type": "Protein", "text": [ "vitamin D receptor" ], "offsets": [ [ 809, 827 ] ], "normalized": [] }, { "id": "PMID-1645452_T6", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 856, 865 ] ], "normalized": [] }, { "id": "PMID-1645452_T7", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 942, 951 ] ], "normalized": [] }, { "id": "PMID-1645452_T8", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 1427, 1436 ] ], "normalized": [] }, { "id": "PMID-1645452_T9", "type": "Protein", "text": [ "IL-1 beta" ], "offsets": [ [ 1553, 1562 ] ], "normalized": [] }, { "id": "PMID-1645452_T10", "type": "Entity", "text": [ "monokine gene" ], "offsets": [ [ 96, 109 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-1645452_1", "entity_ids": [ "PMID-1645452_T2", "PMID-1645452_T3" ] } ]

[]

[ { "id": "PMID-10233882__text", "type": "abstract", "text": [ "An essential role for NF-kappaB in human CD34(+) bone marrow cell survival. \nThe transcription factor, NF-kappaB, is important for T-cell activation, B-cell maturation, and human immunodeficiency virus transcription and plays a role in alternatively mediating and protecting against apoptosis in a variety of cell types. However, a role for NF-kappaB in human CD34(+) bone marrow cells has not been described. We provide evidence here that virtually all human CD34(+) bone marrow cells express NF-kappaB that can be activated by exposure to phorbol 12-myristate 13-acetate and a variety of cytokines, eg, tumor necrosis factor alpha, interleukin-3, and granulocyte-macrophage colony-stimulating factor. In addition, we demonstrate that NF-kappaB may be required for human CD34(+) bone marrow cell clonogenic function and survival. These results offer insight into a new role for NF-kappaB in maintaining survival and function in hematopoietic stem and progenitor cells and suggest that proposed strategies involving inhibition of NF-kappaB activation as an adjunct to cancer chemotherapy should be approached with caution.\n" ], "offsets": [ [ 0, 1123 ] ] } ]

[ { "id": "PMID-10233882_T1", "type": "Protein", "text": [ "CD34" ], "offsets": [ [ 41, 45 ] ], "normalized": [] }, { "id": "PMID-10233882_T2", "type": "Protein", "text": [ "CD34" ], "offsets": [ [ 360, 364 ] ], "normalized": [] }, { "id": "PMID-10233882_T3", "type": "Protein", "text": [ "CD34" ], "offsets": [ [ 460, 464 ] ], "normalized": [] }, { "id": "PMID-10233882_T4", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 605, 632 ] ], "normalized": [] }, { "id": "PMID-10233882_T5", "type": "Protein", "text": [ "interleukin-3" ], "offsets": [ [ 634, 647 ] ], "normalized": [] }, { "id": "PMID-10233882_T6", "type": "Protein", "text": [ "granulocyte-macrophage colony-stimulating factor" ], "offsets": [ [ 653, 701 ] ], "normalized": [] }, { "id": "PMID-10233882_T7", "type": "Protein", "text": [ "CD34" ], "offsets": [ [ 772, 776 ] ], "normalized": [] }, { "id": "PMID-10233882_T8", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 22, 31 ] ], "normalized": [] }, { "id": "PMID-10233882_T9", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 103, 112 ] ], "normalized": [] }, { "id": "PMID-10233882_T10", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 341, 350 ] ], "normalized": [] }, { "id": "PMID-10233882_T11", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 494, 503 ] ], "normalized": [] }, { "id": "PMID-10233882_T12", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 736, 745 ] ], "normalized": [] }, { "id": "PMID-10233882_T13", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 879, 888 ] ], "normalized": [] }, { "id": "PMID-10233882_T14", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1030, 1039 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-8960112__text", "type": "abstract", "text": [ "Lymphocytes from CML patients lack a 47 kDa factor having affinity for a genomic sterol regulatory sequence. \nDeranged cellular cholesterol homeostasis has been widely recognized in the initiation as well as progression of various types of cancers including chronic myeloid leukaemia (CML). Since the human genomic sterol regulatory element (SRE) has been shown to regulate various key genes involved in this phenomenon, the present study revealed the existence of a unique 47 kDa protein factor having affinity for this SRE sequence in lymphocytes from normal subjects, as well as its absence in lymphocytes from untreated CML patients. However, this factor appeared when these CML patients achieved complete haematological remission (CHR) through alpha-interferon therapy. Furthermore, an inverse relationship was also observed between the LDL receptor gene expression at the transcriptional level and the binding affinity of this 47 kDa protein factor to the SRE sequence. Based upon these results we propose that this factor may have a role in pathophysiology of chronic myeloid leukaemia.\n" ], "offsets": [ [ 0, 1094 ] ] } ]

[ { "id": "PMID-8960112_T1", "type": "Protein", "text": [ "LDL receptor" ], "offsets": [ [ 842, 854 ] ], "normalized": [] }, { "id": "PMID-8960112_T2", "type": "Entity", "text": [ "genomic sterol regulatory sequence" ], "offsets": [ [ 73, 107 ] ], "normalized": [] }, { "id": "PMID-8960112_T3", "type": "Entity", "text": [ "human genomic sterol regulatory element" ], "offsets": [ [ 301, 340 ] ], "normalized": [] }, { "id": "PMID-8960112_T4", "type": "Entity", "text": [ "SRE" ], "offsets": [ [ 342, 345 ] ], "normalized": [] }, { "id": "PMID-8960112_T5", "type": "Entity", "text": [ "various key genes" ], "offsets": [ [ 374, 391 ] ], "normalized": [] }, { "id": "PMID-8960112_T6", "type": "Entity", "text": [ "SRE sequence" ], "offsets": [ [ 521, 533 ] ], "normalized": [] }, { "id": "PMID-8960112_T7", "type": "Entity", "text": [ "SRE sequence" ], "offsets": [ [ 962, 974 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-7890658__text", "type": "abstract", "text": [ "Identification of human TR2 orphan receptor response element in the transcriptional initiation site of the simian virus 40 major late promoter [published erratum appears in J Biol Chem 1995 Nov 3;270(44):26721] \nA DNA response element (TR2RE-SV40) for the TR2 orphan receptor, a member of the steroid-thyroid hormone receptor superfamily, has been identified in the simian virus 40 (SV40) +55 region (nucleotide numbers 368-389, 5'-GTTAAGGTTCGTAGGTCATGGA-3'). Electrophoretic mobility shift assay, using in vitro translated TR2 orphan receptor with a molecular mass of 67 kilodaltons, showed a specific binding with high affinity (dissociation constant = 9 nM) for this DNA sequence. DNA-swap experiments using chloramphenicol acetyl-transferase assay demonstrated that androgen can suppress the transcriptional activities of SV40 early promoter via the interaction between this TR2RE-SV40 and the chimeric receptor AR/TR2/AR with the DNA-binding domain of the TR2 orphan receptor flanked by the N-terminal and androgen-binding domains of the androgen receptor. In addition, this TR2RE-SV40 can function as a repressor to suppress the transcriptional activities of both SV40 early and late promoters. Together, these data suggest the TR2RE-SV40 may represent the first identified natural DNA response element for the TR2 orphan receptor that may function as a repressor for the SV40 gene expression.\n" ], "offsets": [ [ 0, 1400 ] ] } ]

[ { "id": "PMID-7890658_T1", "type": "Protein", "text": [ "chloramphenicol acetyl-transferase" ], "offsets": [ [ 711, 745 ] ], "normalized": [] }, { "id": "PMID-7890658_T2", "type": "Entity", "text": [ "human TR2 orphan receptor response element" ], "offsets": [ [ 18, 60 ] ], "normalized": [] }, { "id": "PMID-7890658_T3", "type": "Entity", "text": [ "transcriptional initiation site" ], "offsets": [ [ 68, 99 ] ], "normalized": [] }, { "id": "PMID-7890658_T4", "type": "Entity", "text": [ "simian virus 40 major late promoter" ], "offsets": [ [ 107, 142 ] ], "normalized": [] }, { "id": "PMID-7890658_T5", "type": "Entity", "text": [ "DNA response element" ], "offsets": [ [ 214, 234 ] ], "normalized": [] }, { "id": "PMID-7890658_T6", "type": "Entity", "text": [ "TR2RE-SV40" ], "offsets": [ [ 236, 246 ] ], "normalized": [] }, { "id": "PMID-7890658_T7", "type": "Entity", "text": [ "simian virus 40 (SV40) +55 region" ], "offsets": [ [ 366, 399 ] ], "normalized": [] }, { "id": "PMID-7890658_T8", "type": "Entity", "text": [ "nucleotide numbers 368-389" ], "offsets": [ [ 401, 427 ] ], "normalized": [] }, { "id": "PMID-7890658_T9", "type": "Entity", "text": [ "5'-GTTAAGGTTCGTAGGTCATGGA-3'" ], "offsets": [ [ 429, 457 ] ], "normalized": [] }, { "id": "PMID-7890658_T10", "type": "Entity", "text": [ "DNA sequence" ], "offsets": [ [ 670, 682 ] ], "normalized": [] }, { "id": "PMID-7890658_T11", "type": "Entity", "text": [ "SV40 early promoter" ], "offsets": [ [ 826, 845 ] ], "normalized": [] }, { "id": "PMID-7890658_T12", "type": "Entity", "text": [ "TR2RE-SV40" ], "offsets": [ [ 879, 889 ] ], "normalized": [] }, { "id": "PMID-7890658_T13", "type": "Entity", "text": [ "DNA-binding domain" ], "offsets": [ [ 935, 953 ] ], "normalized": [] }, { "id": "PMID-7890658_T14", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 935, 938 ] ], "normalized": [] }, { "id": "PMID-7890658_T15", "type": "Entity", "text": [ "N-terminal" ], "offsets": [ [ 996, 1006 ] ], "normalized": [] }, { "id": "PMID-7890658_T16", "type": "Entity", "text": [ "androgen-binding domains" ], "offsets": [ [ 1011, 1035 ] ], "normalized": [] }, { "id": "PMID-7890658_T17", "type": "Entity", "text": [ "TR2RE-SV40" ], "offsets": [ [ 1080, 1090 ] ], "normalized": [] }, { "id": "PMID-7890658_T18", "type": "Entity", "text": [ "promoters" ], "offsets": [ [ 1190, 1199 ] ], "normalized": [] }, { "id": "PMID-7890658_T19", "type": "Entity", "text": [ "TR2RE-SV40" ], "offsets": [ [ 1234, 1244 ] ], "normalized": [] }, { "id": "PMID-7890658_T20", "type": "Entity", "text": [ "DNA response element" ], "offsets": [ [ 1288, 1308 ] ], "normalized": [] }, { "id": "PMID-7890658_T21", "type": "Entity", "text": [ "SV40 gene" ], "offsets": [ [ 1378, 1387 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-8871649__text", "type": "abstract", "text": [ "A critical role of Sp1- and Ets-related transcription factors in maintaining CTL-specific expression of the mouse perforin gene. \nThis study was designed to determine the potential cis-elements involved in transcriptional regulation of the mouse perforin gene. DNase I hypersensitive site (DHS) mapping revealed that the perforin locus contained six DHS within 7.0 kb of the 5' upstream sequence (-7.0 kb) and two DHS in intron 2. The six 5' upstream and one intronic DHS were detected in only perforin-expressing lymphocytes. Chloramphenicol acetyltransferase (CAT) activities directed by 5' upstream promoter were detected preferentially in perforin-expressing cell lines. A construct termed PFP5a containing -795 bp exhibited the highest CAT activity, and PFP9a20 containing only -73 bp also produced significantly high CAT activity in CTLL-R8 cells. The proximal region in PFP9a20 contained two potential Sp1 binding sites (GC box and GT box) and one Ets binding site (EBS). Electrophoretic mobility shift assay showed that each of the cis-elements bound specific protein factors. When single-point mutation was introduced to each GC box, EBS, and GT box in PFP9a20, at least 3-fold less CAT activity was observed in CTLL-R8 cells. To confirm the importance of the three cis-acting elements in the perforin gene expression, point mutation was introduced again to each proximal GC box, EBS, and GT box of PFP5a. The point mutations resulted in a 2.5- to 3-fold reduction of CAT activity. The results suggest that a combination of the three proximal cis-acting elements may constitute a minimal region responsible for CTL-specific expression of perforin.\n" ], "offsets": [ [ 0, 1657 ] ] } ]

[ { "id": "PMID-8871649_T1", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 19, 22 ] ], "normalized": [] }, { "id": "PMID-8871649_T2", "type": "Protein", "text": [ "perforin" ], "offsets": [ [ 114, 122 ] ], "normalized": [] }, { "id": "PMID-8871649_T3", "type": "Protein", "text": [ "perforin" ], "offsets": [ [ 246, 254 ] ], "normalized": [] }, { "id": "PMID-8871649_T4", "type": "Protein", "text": [ "perforin" ], "offsets": [ [ 321, 329 ] ], "normalized": [] }, { "id": "PMID-8871649_T5", "type": "Protein", "text": [ "perforin" ], "offsets": [ [ 494, 502 ] ], "normalized": [] }, { "id": "PMID-8871649_T6", "type": "Protein", "text": [ "Chloramphenicol acetyltransferase" ], "offsets": [ [ 527, 560 ] ], "normalized": [] }, { "id": "PMID-8871649_T7", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 562, 565 ] ], "normalized": [] }, { "id": "PMID-8871649_T8", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 741, 744 ] ], "normalized": [] }, { "id": "PMID-8871649_T9", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 823, 826 ] ], "normalized": [] }, { "id": "PMID-8871649_T10", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 909, 912 ] ], "normalized": [] }, { "id": "PMID-8871649_T11", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1192, 1195 ] ], "normalized": [] }, { "id": "PMID-8871649_T12", "type": "Protein", "text": [ "perforin" ], "offsets": [ [ 1302, 1310 ] ], "normalized": [] }, { "id": "PMID-8871649_T13", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 1477, 1480 ] ], "normalized": [] }, { "id": "PMID-8871649_T14", "type": "Protein", "text": [ "perforin" ], "offsets": [ [ 1647, 1655 ] ], "normalized": [] }, { "id": "PMID-8871649_T15", "type": "Entity", "text": [ "cis-elements" ], "offsets": [ [ 181, 193 ] ], "normalized": [] }, { "id": "PMID-8871649_T16", "type": "Entity", "text": [ "DNase I hypersensitive site" ], "offsets": [ [ 261, 288 ] ], "normalized": [] }, { "id": "PMID-8871649_T17", "type": "Entity", "text": [ "DHS" ], "offsets": [ [ 290, 293 ] ], "normalized": [] }, { "id": "PMID-8871649_T18", "type": "Entity", "text": [ "locus" ], "offsets": [ [ 330, 335 ] ], "normalized": [] }, { "id": "PMID-8871649_T19", "type": "Entity", "text": [ "DHS" ], "offsets": [ [ 350, 353 ] ], "normalized": [] }, { "id": "PMID-8871649_T20", "type": "Entity", "text": [ "5' upstream sequence" ], "offsets": [ [ 375, 395 ] ], "normalized": [] }, { "id": "PMID-8871649_T21", "type": "Entity", "text": [ "DHS" ], "offsets": [ [ 414, 417 ] ], "normalized": [] }, { "id": "PMID-8871649_T22", "type": "Entity", "text": [ "intron 2" ], "offsets": [ [ 421, 429 ] ], "normalized": [] }, { "id": "PMID-8871649_T23", "type": "Entity", "text": [ "5' upstream" ], "offsets": [ [ 439, 450 ] ], "normalized": [] }, { "id": "PMID-8871649_T24", "type": "Entity", "text": [ "intronic DHS" ], "offsets": [ [ 459, 471 ] ], "normalized": [] }, { "id": "PMID-8871649_T25", "type": "Entity", "text": [ "5' upstream promoter" ], "offsets": [ [ 590, 610 ] ], "normalized": [] }, { "id": "PMID-8871649_T26", "type": "Entity", "text": [ "-795 bp" ], "offsets": [ [ 711, 718 ] ], "normalized": [] }, { "id": "PMID-8871649_T27", "type": "Entity", "text": [ "-73 bp" ], "offsets": [ [ 783, 789 ] ], "normalized": [] }, { "id": "PMID-8871649_T28", "type": "Entity", "text": [ "proximal region" ], "offsets": [ [ 858, 873 ] ], "normalized": [] }, { "id": "PMID-8871649_T29", "type": "Entity", "text": [ "binding sites" ], "offsets": [ [ 913, 926 ] ], "normalized": [] }, { "id": "PMID-8871649_T30", "type": "Entity", "text": [ "GC box" ], "offsets": [ [ 928, 934 ] ], "normalized": [] }, { "id": "PMID-8871649_T31", "type": "Entity", "text": [ "GT box" ], "offsets": [ [ 939, 945 ] ], "normalized": [] }, { "id": "PMID-8871649_T32", "type": "Entity", "text": [ "Ets binding site" ], "offsets": [ [ 955, 971 ] ], "normalized": [] }, { "id": "PMID-8871649_T33", "type": "Entity", "text": [ "EBS" ], "offsets": [ [ 973, 976 ] ], "normalized": [] }, { "id": "PMID-8871649_T34", "type": "Entity", "text": [ "cis-elements" ], "offsets": [ [ 1040, 1052 ] ], "normalized": [] }, { "id": "PMID-8871649_T35", "type": "Entity", "text": [ "GC box" ], "offsets": [ [ 1135, 1141 ] ], "normalized": [] }, { "id": "PMID-8871649_T36", "type": "Entity", "text": [ "EBS" ], "offsets": [ [ 1143, 1146 ] ], "normalized": [] }, { "id": "PMID-8871649_T37", "type": "Entity", "text": [ "GT box" ], "offsets": [ [ 1152, 1158 ] ], "normalized": [] }, { "id": "PMID-8871649_T38", "type": "Entity", "text": [ "cis-acting elements" ], "offsets": [ [ 1275, 1294 ] ], "normalized": [] }, { "id": "PMID-8871649_T39", "type": "Entity", "text": [ "proximal GC box" ], "offsets": [ [ 1372, 1387 ] ], "normalized": [] }, { "id": "PMID-8871649_T40", "type": "Entity", "text": [ "EBS" ], "offsets": [ [ 1389, 1392 ] ], "normalized": [] }, { "id": "PMID-8871649_T41", "type": "Entity", "text": [ "GT box" ], "offsets": [ [ 1398, 1404 ] ], "normalized": [] }, { "id": "PMID-8871649_T42", "type": "Entity", "text": [ "cis-acting elements" ], "offsets": [ [ 1552, 1571 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-8871649_1", "entity_ids": [ "PMID-8871649_T6", "PMID-8871649_T7" ] } ]

[ { "id": "PMID-8871649_R1", "type": "Protein-Component", "arg1_id": "PMID-8871649_T3", "arg2_id": "PMID-8871649_T15", "normalized": [] }, { "id": "PMID-8871649_R2", "type": "Protein-Component", "arg1_id": "PMID-8871649_T4", "arg2_id": "PMID-8871649_T21", "normalized": [] }, { "id": "PMID-8871649_R3", "type": "Protein-Component", "arg1_id": "PMID-8871649_T4", "arg2_id": "PMID-8871649_T22", "normalized": [] }, { "id": "PMID-8871649_R4", "type": "Protein-Component", "arg1_id": "PMID-8871649_T4", "arg2_id": "PMID-8871649_T19", "normalized": [] }, { "id": "PMID-8871649_R5", "type": "Protein-Component", "arg1_id": "PMID-8871649_T4", "arg2_id": "PMID-8871649_T20", "normalized": [] }, { "id": "PMID-8871649_R6", "type": "Protein-Component", "arg1_id": "PMID-8871649_T12", "arg2_id": "PMID-8871649_T38", "normalized": [] }, { "id": "PMID-8871649_R7", "type": "Protein-Component", "arg1_id": "PMID-8871649_T14", "arg2_id": "PMID-8871649_T42", "normalized": [] } ]

[ { "id": "PMID-7525701__text", "type": "abstract", "text": [ "Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. \nThe B cell-associated surface molecule CD40 functions to regulate B cell responses. Cross-linking CD40 on B cells can lead to homotypic cell adhesion, IL-6 production, and, in combination with cytokines, to Ig isotype switching. Tyrosine kinase activity is increased shortly after engagement of this receptor. Little is known about how the very early events induced by CD40 cross-linking link to cellular responses. In this study, we demonstrate that nuclear factor (NF)-kappa B and NF-kappa B-like transcription factors are activated after cross-linking CD40 on resting human tonsillar B cells and on B cell lines. The activation is rapid and is mediated through a tyrosine kinase-dependent pathway. The complexes detected in electrophoretic mobility shift assays contain p50, p65 (RelA), c-Rel, and most likely other components. By using transient transfection assays, we found that cross-linking CD40 supports NF-kappa B-dependent gene expression. Our results define the NF-kappa B system as an intermediate event in CD40 signaling and suggest that the CD40 pathway can influence the expression of B cell-associated genes with NF-kappa B consensus sites.\n" ], "offsets": [ [ 0, 1231 ] ] } ]

[ { "id": "PMID-7525701_T1", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 14, 18 ] ], "normalized": [] }, { "id": "PMID-7525701_T2", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 112, 116 ] ], "normalized": [] }, { "id": "PMID-7525701_T3", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 171, 175 ] ], "normalized": [] }, { "id": "PMID-7525701_T4", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 224, 228 ] ], "normalized": [] }, { "id": "PMID-7525701_T5", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 442, 446 ] ], "normalized": [] }, { "id": "PMID-7525701_T6", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 628, 632 ] ], "normalized": [] }, { "id": "PMID-7525701_T7", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 846, 849 ] ], "normalized": [] }, { "id": "PMID-7525701_T8", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 851, 854 ] ], "normalized": [] }, { "id": "PMID-7525701_T9", "type": "Protein", "text": [ "RelA" ], "offsets": [ [ 856, 860 ] ], "normalized": [] }, { "id": "PMID-7525701_T10", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 863, 868 ] ], "normalized": [] }, { "id": "PMID-7525701_T11", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 972, 976 ] ], "normalized": [] }, { "id": "PMID-7525701_T12", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 1093, 1097 ] ], "normalized": [] }, { "id": "PMID-7525701_T13", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 1129, 1133 ] ], "normalized": [] }, { "id": "PMID-7525701_T14", "type": "Entity", "text": [ "nuclear factor-kappa B" ], "offsets": [ [ 48, 70 ] ], "normalized": [] }, { "id": "PMID-7525701_T15", "type": "Entity", "text": [ "Tyrosine" ], "offsets": [ [ 302, 310 ] ], "normalized": [] }, { "id": "PMID-7525701_T16", "type": "Entity", "text": [ "nuclear factor (NF)-kappa B" ], "offsets": [ [ 524, 551 ] ], "normalized": [] }, { "id": "PMID-7525701_T17", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 986, 996 ] ], "normalized": [] }, { "id": "PMID-7525701_T18", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1047, 1057 ] ], "normalized": [] }, { "id": "PMID-7525701_T19", "type": "Entity", "text": [ "B cell-associated genes with NF-kappa B consensus sites" ], "offsets": [ [ 1174, 1229 ] ], "normalized": [] }, { "id": "PMID-7525701_T20", "type": "Entity", "text": [ "B cell-associated genes" ], "offsets": [ [ 1174, 1197 ] ], "normalized": [] }, { "id": "PMID-7525701_T21", "type": "Entity", "text": [ "NF-kappa B consensus sites" ], "offsets": [ [ 1203, 1229 ] ], "normalized": [] }, { "id": "PMID-7525701_T22", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1203, 1213 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-7525701_1", "entity_ids": [ "PMID-7525701_T8", "PMID-7525701_T9" ] } ]

[]

[ { "id": "PMID-2278044__text", "type": "abstract", "text": [ "Functional analysis of cis-linked regulatory sequences in the HLA DRA promoter by transcription in vitro. \nTwo consensus sequences, called X and Y boxes, capable of binding nuclear proteins and regulating expression in B cells have been defined within the immediate upstream region of major histocompatibility complex (MHC) class II promoters. Unlike other class II promoters, the HLA-DR alpha (DRA) promoter also contains one element identical to the \"octamer\" motif of immunoglobulin variable region promoters that is responsible for B cell-specific transcription. This \"octamer\" in the context of DRA appears capable of binding both the ubiquitous (OTF-1) and lymphoid-specific (OTF-2) \"octamer\" binding proteins, but at least one other distinct \"octamer\" complex was found. In order to characterize the function of cis-acting elements, we have developed an in vitro system in which a DRA promoter construct is transcribed more efficiently in extracts from B cells than in extracts from class II-negative HeLa cells. 5' deletion constructs which lacked the Y box, but retained the \"octamer\" motif and TATA box were completely inactive, and internal deletion of the Y box reduced transcription by 95%. Using supercoiled, but not linear templates, we observed differences in transcription efficiencies from templates lacking or disrupting the X consensus element that reflect effects of random replacement of X box sequences in transient expression assays. Demonstration of the complete dependence on the Y box in this system suggests that, despite its demonstrated importance in the DRA promoter, the DRA \"octamer\" does not utilize OTF-2 in a manner analogous to immunoglobulin promoters in B cells.\n" ], "offsets": [ [ 0, 1702 ] ] } ]

[ { "id": "PMID-2278044_T1", "type": "Protein", "text": [ "OTF-1" ], "offsets": [ [ 652, 657 ] ], "normalized": [] }, { "id": "PMID-2278044_T2", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 682, 687 ] ], "normalized": [] }, { "id": "PMID-2278044_T3", "type": "Protein", "text": [ "OTF-2" ], "offsets": [ [ 1634, 1639 ] ], "normalized": [] }, { "id": "PMID-2278044_T4", "type": "Entity", "text": [ "cis-linked regulatory sequences" ], "offsets": [ [ 23, 54 ] ], "normalized": [] }, { "id": "PMID-2278044_T5", "type": "Entity", "text": [ "HLA DRA promoter" ], "offsets": [ [ 62, 78 ] ], "normalized": [] }, { "id": "PMID-2278044_T6", "type": "Entity", "text": [ "X" ], "offsets": [ [ 139, 140 ] ], "normalized": [] }, { "id": "PMID-2278044_T7", "type": "Entity", "text": [ "Y boxes" ], "offsets": [ [ 145, 152 ] ], "normalized": [] }, { "id": "PMID-2278044_T8", "type": "Entity", "text": [ "major histocompatibility complex (MHC) class II promoters" ], "offsets": [ [ 285, 342 ] ], "normalized": [] }, { "id": "PMID-2278044_T9", "type": "Entity", "text": [ "class II promoters" ], "offsets": [ [ 357, 375 ] ], "normalized": [] }, { "id": "PMID-2278044_T10", "type": "Entity", "text": [ "HLA-DR alpha (DRA) promoter" ], "offsets": [ [ 381, 408 ] ], "normalized": [] }, { "id": "PMID-2278044_T11", "type": "Entity", "text": [ "\"octamer\" motif" ], "offsets": [ [ 452, 467 ] ], "normalized": [] }, { "id": "PMID-2278044_T12", "type": "Entity", "text": [ "immunoglobulin variable region promoters" ], "offsets": [ [ 471, 511 ] ], "normalized": [] }, { "id": "PMID-2278044_T13", "type": "Entity", "text": [ "octamer" ], "offsets": [ [ 573, 580 ] ], "normalized": [] }, { "id": "PMID-2278044_T14", "type": "Entity", "text": [ "\"octamer\" complex" ], "offsets": [ [ 749, 766 ] ], "normalized": [] }, { "id": "PMID-2278044_T15", "type": "Entity", "text": [ "cis-acting elements" ], "offsets": [ [ 819, 838 ] ], "normalized": [] }, { "id": "PMID-2278044_T16", "type": "Entity", "text": [ "5' deletion constructs" ], "offsets": [ [ 1020, 1042 ] ], "normalized": [] }, { "id": "PMID-2278044_T17", "type": "Entity", "text": [ "Y box" ], "offsets": [ [ 1060, 1065 ] ], "normalized": [] }, { "id": "PMID-2278044_T18", "type": "Entity", "text": [ "\"octamer\" motif" ], "offsets": [ [ 1084, 1099 ] ], "normalized": [] }, { "id": "PMID-2278044_T19", "type": "Entity", "text": [ "TATA box" ], "offsets": [ [ 1104, 1112 ] ], "normalized": [] }, { "id": "PMID-2278044_T20", "type": "Entity", "text": [ "Y box" ], "offsets": [ [ 1168, 1173 ] ], "normalized": [] }, { "id": "PMID-2278044_T21", "type": "Entity", "text": [ "X consensus element" ], "offsets": [ [ 1344, 1363 ] ], "normalized": [] }, { "id": "PMID-2278044_T22", "type": "Entity", "text": [ "X box sequences" ], "offsets": [ [ 1410, 1425 ] ], "normalized": [] }, { "id": "PMID-2278044_T23", "type": "Entity", "text": [ "Y box" ], "offsets": [ [ 1506, 1511 ] ], "normalized": [] }, { "id": "PMID-2278044_T24", "type": "Entity", "text": [ "DRA promoter" ], "offsets": [ [ 1585, 1597 ] ], "normalized": [] }, { "id": "PMID-2278044_T25", "type": "Entity", "text": [ "DRA \"octamer\"" ], "offsets": [ [ 1603, 1616 ] ], "normalized": [] }, { "id": "PMID-2278044_T26", "type": "Entity", "text": [ "immunoglobulin promoters" ], "offsets": [ [ 1665, 1689 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-9765295__text", "type": "abstract", "text": [ "Fcgamma receptor-mediated mitogen-activated protein kinase activation in monocytes is independent of Ras. \nReceptors for the Fc portion of immunoglobulin molecules (FcR) present on leukocyte cell membranes mediate a large number of cellular responses that are very important in host defense, including phagocytosis, cell cytotoxicity, production and secretion of inflammatory mediators, and modulation of the immune response. Cross-linking of FcR with immune complexes leads, first to activation of protein-tyrosine kinases. The molecular events that follow and that transduce signals from these receptors to the nucleus are still poorly defined. We have investigated the signal transduction pathway from Fc receptors that leads to gene activation and production of cytokines in monocytes. Cross-linking of FcR, on the THP-1 monocytic cell line, by immune complexes resulted in both activation of the transcription factor NF-kappaB and interleukin 1 production. These responses were completely blocked by tyrosine kinase inhibitors. In contrast, expression of dominant negative mutants of Ras and Raf-1, in these cells, did not have any effect on FcR-mediated nuclear factor activation, suggesting that the mitogen-activated protein kinase (MAPK) signaling pathway was not used by these receptors. However, MAPK activation was easily detected by in vitro kinase assays, after FcR cross-linking with immune complexes. Using the specific MAPK/extracellular signal-regulated kinase kinase (MAPK kinase) inhibitor PD98059, we found that MAPK activation is necessary for FcR-dependent activation of the nuclear factor NF-kappaB. These results strongly suggest that the signaling pathway from Fc receptors leading to expression of different genes important to leukocyte biology, initiates with tyrosine kinases and requires MAPK activation; but in contrast to other tyrosine kinase receptors, FcR-mediated MAPK activation does not involve Ras and Raf.\n" ], "offsets": [ [ 0, 1946 ] ] } ]

[ { "id": "PMID-9765295_T1", "type": "Protein", "text": [ "Raf-1" ], "offsets": [ [ 1097, 1102 ] ], "normalized": [] }, { "id": "PMID-9765295_T2", "type": "Entity", "text": [ "Fc portion" ], "offsets": [ [ 125, 135 ] ], "normalized": [] }, { "id": "PMID-9765295_T3", "type": "Entity", "text": [ "immune complexes" ], "offsets": [ [ 452, 468 ] ], "normalized": [] }, { "id": "PMID-9765295_T4", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 507, 515 ] ], "normalized": [] }, { "id": "PMID-9765295_T5", "type": "Entity", "text": [ "immune complexes" ], "offsets": [ [ 849, 865 ] ], "normalized": [] }, { "id": "PMID-9765295_T6", "type": "Entity", "text": [ "transcription factor" ], "offsets": [ [ 901, 921 ] ], "normalized": [] }, { "id": "PMID-9765295_T7", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 922, 931 ] ], "normalized": [] }, { "id": "PMID-9765295_T8", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 1005, 1013 ] ], "normalized": [] }, { "id": "PMID-9765295_T9", "type": "Entity", "text": [ "immune complexes" ], "offsets": [ [ 1399, 1415 ] ], "normalized": [] }, { "id": "PMID-9765295_T10", "type": "Entity", "text": [ "nuclear factor" ], "offsets": [ [ 1598, 1612 ] ], "normalized": [] }, { "id": "PMID-9765295_T11", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1613, 1622 ] ], "normalized": [] }, { "id": "PMID-9765295_T12", "type": "Entity", "text": [ "genes" ], "offsets": [ [ 1735, 1740 ] ], "normalized": [] }, { "id": "PMID-9765295_T13", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 1788, 1796 ] ], "normalized": [] }, { "id": "PMID-9765295_T14", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 1860, 1868 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-1956769__text", "type": "abstract", "text": [ "Identification of transcriptional suppressor proteins that bind to the negative regulatory element of the human immunodeficiency virus type 1. \nTwo different proteins which independently bound to neighboring sequences within the negative regulatory element (NRE) of human immunodeficiency virus type 1 (HIV-1) were detected in the nuclear extract of a virus-infected human T cell line. One of the factors bound to a novel dyad symmetrical sequence. This sequence is well conserved in various HIV-1 isolates and partial homology was found with the promoter region of the human retinoblastoma gene. Similar DNA binding activity was detected in a variety of virus-uninfected human T cell lines and HeLa cells by means of a gel mobility shift assay. The other factor bound to a putative AP-1 recognition sequence predicted for the HIV-1 NRE. However, this factor did not bind to a typical AP-1 site. The insertion of multiple copies of the binding site for the former or latter factor into a heterologous promoter reduced the promoter activity to one-tenth or one-third, respectively. Thus, each factor may function as a novel negative regulator of transcription.\n" ], "offsets": [ [ 0, 1160 ] ] } ]

[ { "id": "PMID-1956769_T1", "type": "Entity", "text": [ "negative regulatory element" ], "offsets": [ [ 71, 98 ] ], "normalized": [] }, { "id": "PMID-1956769_T2", "type": "Entity", "text": [ "neighboring sequences" ], "offsets": [ [ 196, 217 ] ], "normalized": [] }, { "id": "PMID-1956769_T3", "type": "Entity", "text": [ "negative regulatory element" ], "offsets": [ [ 229, 256 ] ], "normalized": [] }, { "id": "PMID-1956769_T4", "type": "Entity", "text": [ "NRE" ], "offsets": [ [ 258, 261 ] ], "normalized": [] }, { "id": "PMID-1956769_T5", "type": "Entity", "text": [ "HIV-1" ], "offsets": [ [ 303, 308 ] ], "normalized": [] }, { "id": "PMID-1956769_T6", "type": "Entity", "text": [ "novel dyad symmetrical sequence" ], "offsets": [ [ 416, 447 ] ], "normalized": [] }, { "id": "PMID-1956769_T7", "type": "Entity", "text": [ "promoter region" ], "offsets": [ [ 547, 562 ] ], "normalized": [] }, { "id": "PMID-1956769_T8", "type": "Entity", "text": [ "human retinoblastoma gene" ], "offsets": [ [ 570, 595 ] ], "normalized": [] }, { "id": "PMID-1956769_T9", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 605, 608 ] ], "normalized": [] }, { "id": "PMID-1956769_T10", "type": "Entity", "text": [ "putative AP-1 recognition sequence" ], "offsets": [ [ 774, 808 ] ], "normalized": [] }, { "id": "PMID-1956769_T11", "type": "Entity", "text": [ "HIV-1 NRE" ], "offsets": [ [ 827, 836 ] ], "normalized": [] }, { "id": "PMID-1956769_T12", "type": "Entity", "text": [ "AP-1 site" ], "offsets": [ [ 885, 894 ] ], "normalized": [] }, { "id": "PMID-1956769_T13", "type": "Entity", "text": [ "binding site" ], "offsets": [ [ 936, 948 ] ], "normalized": [] }, { "id": "PMID-1956769_T14", "type": "Entity", "text": [ "heterologous promoter" ], "offsets": [ [ 988, 1009 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-7635985__text", "type": "abstract", "text": [ "Interleukin 4 activates a signal transducer and activator of transcription (Stat) protein which interacts with an interferon-gamma activation site-like sequence upstream of the I epsilon exon in a human B cell line. Evidence for the involvement of Janus kinase 3 and interleukin-4 Stat. \nGerm line C transcripts can be induced by IL-4 in the human B cell line, BL-2. Utilizing a IFN-gamma activation site-like DNA sequence element located upstream of the I epsilon exon, we demonstrated by gel mobility shift assays that IL-4 induced a binding activity in the cytosol and nucleus of BL-2 cells. This factor was designated IL-4 NAF (IL-4-induced nuclear-activating factors) and was identified as a tyrosine phosphoprotein, which translocates from the cytosol to the nucleus upon IL-4 treatment. Because these are the characteristics of a signal transducer and activator of transcription (Stat) protein, we determined whether antibodies to Stat proteins will interfere with gel mobility shift and found that antibodies to IL-4 Stat, also known as Stat6, but not antibodies to other Stat proteins, interfere with the formation of the IL-4 NAF complex. Congruous with the involvement of a Stat protein, IL-4 induced robust Janus kinase 3 (JAK3) activity in BL-2 cells. Cotransfection of JAK3 with IL-4 Stat into COS-7 cells produced an intracellular activity which bound the same IFN-gamma activation site-like sequence and comigrated with IL-4 NAF in electrophoretic mobility shift assay. These results show that IL-4 NAF is IL-4 Stat, which is activated by JAK3 in response to IL-4 receptor engagement.\n" ], "offsets": [ [ 0, 1601 ] ] } ]

[ { "id": "PMID-7635985_T1", "type": "Protein", "text": [ "Interleukin 4" ], "offsets": [ [ 0, 13 ] ], "normalized": [] }, { "id": "PMID-7635985_T2", "type": "Protein", "text": [ "interferon-gamma" ], "offsets": [ [ 114, 130 ] ], "normalized": [] }, { "id": "PMID-7635985_T3", "type": "Protein", "text": [ "Janus kinase 3" ], "offsets": [ [ 248, 262 ] ], "normalized": [] }, { "id": "PMID-7635985_T4", "type": "Protein", "text": [ "interleukin-4" ], "offsets": [ [ 267, 280 ] ], "normalized": [] }, { "id": "PMID-7635985_T5", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 330, 334 ] ], "normalized": [] }, { "id": "PMID-7635985_T6", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 379, 388 ] ], "normalized": [] }, { "id": "PMID-7635985_T7", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 521, 525 ] ], "normalized": [] }, { "id": "PMID-7635985_T8", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 622, 626 ] ], "normalized": [] }, { "id": "PMID-7635985_T9", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 632, 636 ] ], "normalized": [] }, { "id": "PMID-7635985_T10", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 778, 782 ] ], "normalized": [] }, { "id": "PMID-7635985_T11", "type": "Protein", "text": [ "IL-4 Stat" ], "offsets": [ [ 1020, 1029 ] ], "normalized": [] }, { "id": "PMID-7635985_T12", "type": "Protein", "text": [ "Stat6" ], "offsets": [ [ 1045, 1050 ] ], "normalized": [] }, { "id": "PMID-7635985_T13", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1131, 1135 ] ], "normalized": [] }, { "id": "PMID-7635985_T14", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1199, 1203 ] ], "normalized": [] }, { "id": "PMID-7635985_T15", "type": "Protein", "text": [ "Janus kinase 3" ], "offsets": [ [ 1219, 1233 ] ], "normalized": [] }, { "id": "PMID-7635985_T16", "type": "Protein", "text": [ "JAK3" ], "offsets": [ [ 1235, 1239 ] ], "normalized": [] }, { "id": "PMID-7635985_T17", "type": "Protein", "text": [ "JAK3" ], "offsets": [ [ 1283, 1287 ] ], "normalized": [] }, { "id": "PMID-7635985_T18", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1293, 1297 ] ], "normalized": [] }, { "id": "PMID-7635985_T19", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1376, 1385 ] ], "normalized": [] }, { "id": "PMID-7635985_T20", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1436, 1440 ] ], "normalized": [] }, { "id": "PMID-7635985_T21", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1510, 1514 ] ], "normalized": [] }, { "id": "PMID-7635985_T22", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1522, 1526 ] ], "normalized": [] }, { "id": "PMID-7635985_T23", "type": "Protein", "text": [ "JAK3" ], "offsets": [ [ 1555, 1559 ] ], "normalized": [] }, { "id": "PMID-7635985_T24", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1575, 1579 ] ], "normalized": [] }, { "id": "PMID-7635985_T25", "type": "Entity", "text": [ "activation site-like sequence" ], "offsets": [ [ 131, 160 ] ], "normalized": [] }, { "id": "PMID-7635985_T26", "type": "Entity", "text": [ "I epsilon exon" ], "offsets": [ [ 177, 191 ] ], "normalized": [] }, { "id": "PMID-7635985_T27", "type": "Entity", "text": [ "activation site-like DNA sequence element" ], "offsets": [ [ 389, 430 ] ], "normalized": [] }, { "id": "PMID-7635985_T28", "type": "Entity", "text": [ "I epsilon exon" ], "offsets": [ [ 455, 469 ] ], "normalized": [] }, { "id": "PMID-7635985_T29", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 697, 705 ] ], "normalized": [] }, { "id": "PMID-7635985_T30", "type": "Entity", "text": [ "NAF complex" ], "offsets": [ [ 1136, 1147 ] ], "normalized": [] }, { "id": "PMID-7635985_T31", "type": "Entity", "text": [ "activation site-like sequence" ], "offsets": [ [ 1386, 1415 ] ], "normalized": [] }, { "id": "PMID-7635985_T32", "type": "Entity", "text": [ "NAF" ], "offsets": [ [ 1441, 1444 ] ], "normalized": [] }, { "id": "PMID-7635985_T33", "type": "Entity", "text": [ "NAF" ], "offsets": [ [ 1515, 1518 ] ], "normalized": [] }, { "id": "PMID-7635985_T34", "type": "Entity", "text": [ "receptor" ], "offsets": [ [ 1580, 1588 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-7635985_1", "entity_ids": [ "PMID-7635985_T11", "PMID-7635985_T12" ] }, { "id": "PMID-7635985_2", "entity_ids": [ "PMID-7635985_T15", "PMID-7635985_T16" ] } ]

[ { "id": "PMID-7635985_R1", "type": "Protein-Component", "arg1_id": "PMID-7635985_T2", "arg2_id": "PMID-7635985_T25", "normalized": [] }, { "id": "PMID-7635985_R2", "type": "Subunit-Complex", "arg1_id": "PMID-7635985_T13", "arg2_id": "PMID-7635985_T30", "normalized": [] }, { "id": "PMID-7635985_R3", "type": "Protein-Component", "arg1_id": "PMID-7635985_T19", "arg2_id": "PMID-7635985_T31", "normalized": [] }, { "id": "PMID-7635985_R4", "type": "Subunit-Complex", "arg1_id": "PMID-7635985_T20", "arg2_id": "PMID-7635985_T32", "normalized": [] }, { "id": "PMID-7635985_R5", "type": "Subunit-Complex", "arg1_id": "PMID-7635985_T21", "arg2_id": "PMID-7635985_T33", "normalized": [] } ]

[ { "id": "PMID-9428992__text", "type": "abstract", "text": [ "Constitutive expression c-fos, c-jun, and NF kappa B mRNA is in nucleated fetal blood cells and up-regulation of c-fos and c-jun with anti-CD3 stimulation. \nFetal and neonatal lymphocytes are relatively resistant to activation and cytokine production when stimulated either via their T-cell antigen receptors or lectins. The molecular mechanism(s) responsible for this phenomenon have not been clearly elucidated. We have hypothesized that such defects in fetal/neonatal T-cell activation may be due to lack of expression of the transcriptional regulatory elements required for T-cell activation. We used reverse transcriptase-polymerase chain reaction to examine both fetal and term neonatal cord bloods for mRNA expression of three transcription factors implicated in T-cell activation: c-jun, c-fos, and NF kappa B (p50 subunit). We demonstrate that mRNAs for all three of these regulatory factors are expressed in fetal blood cells by the 27th week of gestation and in term cord bloods. Activation of term infant cord blood mononuclear cells with anti-CD3 monoclonal antibodies resulted in up-regulation of both c-jun and c-fos mRNAs within 15 min of stimulation. However, secretion of IL-2 by anti-CD3-stimulated cord blood mononuclear cells was still blunted compared with control cells from adults. We conclude that fetal nucleated blood cells constitutively express important genes for cytokine regulation and are able to increase intracellular accumulation of the mRNAs for these factors in response to anti-CD3 stimulation. Thus, qualitative differences in the capacity to regulate these factors could not be shown in fetal blood cells. Quantitative experiments comparing binding of these transcription factors to the IL-2 promoter are currently under investigation.\n" ], "offsets": [ [ 0, 1777 ] ] } ]

[ { "id": "PMID-9428992_T1", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 24, 29 ] ], "normalized": [] }, { "id": "PMID-9428992_T2", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 31, 36 ] ], "normalized": [] }, { "id": "PMID-9428992_T3", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 113, 118 ] ], "normalized": [] }, { "id": "PMID-9428992_T4", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 123, 128 ] ], "normalized": [] }, { "id": "PMID-9428992_T5", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 789, 794 ] ], "normalized": [] }, { "id": "PMID-9428992_T6", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 796, 801 ] ], "normalized": [] }, { "id": "PMID-9428992_T7", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 819, 822 ] ], "normalized": [] }, { "id": "PMID-9428992_T8", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1116, 1121 ] ], "normalized": [] }, { "id": "PMID-9428992_T9", "type": "Protein", "text": [ "c-fos" ], "offsets": [ [ 1126, 1131 ] ], "normalized": [] }, { "id": "PMID-9428992_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1190, 1194 ] ], "normalized": [] }, { "id": "PMID-9428992_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1728, 1732 ] ], "normalized": [] }, { "id": "PMID-9428992_T12", "type": "Entity", "text": [ "CD3" ], "offsets": [ [ 139, 142 ] ], "normalized": [] }, { "id": "PMID-9428992_T13", "type": "Entity", "text": [ "NF kappa B" ], "offsets": [ [ 807, 817 ] ], "normalized": [] }, { "id": "PMID-9428992_T14", "type": "Entity", "text": [ "CD3" ], "offsets": [ [ 1056, 1059 ] ], "normalized": [] }, { "id": "PMID-9428992_T15", "type": "Entity", "text": [ "CD3" ], "offsets": [ [ 1203, 1206 ] ], "normalized": [] }, { "id": "PMID-9428992_T16", "type": "Entity", "text": [ "genes" ], "offsets": [ [ 1384, 1389 ] ], "normalized": [] }, { "id": "PMID-9428992_T17", "type": "Entity", "text": [ "CD3" ], "offsets": [ [ 1517, 1520 ] ], "normalized": [] }, { "id": "PMID-9428992_T18", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1733, 1741 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-9428992_R1", "type": "Subunit-Complex", "arg1_id": "PMID-9428992_T7", "arg2_id": "PMID-9428992_T13", "normalized": [] }, { "id": "PMID-9428992_R2", "type": "Protein-Component", "arg1_id": "PMID-9428992_T11", "arg2_id": "PMID-9428992_T18", "normalized": [] } ]

[ { "id": "PMID-9725220__text", "type": "abstract", "text": [ "Transcription of a minimal promoter from the NF-IL6 gene is regulated by CREB/ATF and SP1 proteins in U937 promonocytic cells. \nNF-IL6 is an important transcriptional regulator of genes induced in activated monocytes/macrophages, and NF-IL6 is the only CCAAT/enhancer-binding protein (C/EBP) family member whose steady-state mRNA levels increase upon activation of monocytes (1). We show that increased transcription of the NF-IL6 gene is responsible, at least in part, for induction of NF-IL6 mRNA following activation of U937 promonocytic cells. We have identified a 104-bp minimal promoter region of the NF-IL6 gene that is sufficient for basal and activation-dependent induction of transcription in U937 cells. This region contains binding sites for the cAMP response element-binding protein/activation transcription factor (CREB/ATF) and Sp1 families of transcription factors. Each site is functionally important and contributes independently to transcription of the NF-IL6 gene in U937 cells.\n" ], "offsets": [ [ 0, 999 ] ] } ]

[ { "id": "PMID-9725220_T1", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 45, 51 ] ], "normalized": [] }, { "id": "PMID-9725220_T2", "type": "Protein", "text": [ "SP1" ], "offsets": [ [ 86, 89 ] ], "normalized": [] }, { "id": "PMID-9725220_T3", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 128, 134 ] ], "normalized": [] }, { "id": "PMID-9725220_T4", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 234, 240 ] ], "normalized": [] }, { "id": "PMID-9725220_T5", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 424, 430 ] ], "normalized": [] }, { "id": "PMID-9725220_T6", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 487, 493 ] ], "normalized": [] }, { "id": "PMID-9725220_T7", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 607, 613 ] ], "normalized": [] }, { "id": "PMID-9725220_T8", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 843, 846 ] ], "normalized": [] }, { "id": "PMID-9725220_T9", "type": "Protein", "text": [ "NF-IL6" ], "offsets": [ [ 972, 978 ] ], "normalized": [] }, { "id": "PMID-9725220_T10", "type": "Entity", "text": [ "minimal promoter" ], "offsets": [ [ 19, 35 ] ], "normalized": [] }, { "id": "PMID-9725220_T11", "type": "Entity", "text": [ "genes" ], "offsets": [ [ 180, 185 ] ], "normalized": [] }, { "id": "PMID-9725220_T12", "type": "Entity", "text": [ "104-bp minimal promoter region" ], "offsets": [ [ 569, 599 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-9725220_R1", "type": "Protein-Component", "arg1_id": "PMID-9725220_T1", "arg2_id": "PMID-9725220_T10", "normalized": [] }, { "id": "PMID-9725220_R2", "type": "Protein-Component", "arg1_id": "PMID-9725220_T7", "arg2_id": "PMID-9725220_T12", "normalized": [] } ]

[ { "id": "PMID-2105946__text", "type": "abstract", "text": [ "Transcriptional and post-transcriptional regulation of c-jun expression during monocytic differentiation of human myeloid leukemic cells. \nAP-1, the polypeptide product of c-jun, recognizes and binds to specific DNA sequences and stimulates transcription of genes responsive to certain growth factors and phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). We studied the effects of TPA on the regulation of c-jun gene expression in HL-60 cells during monocytic differentiation. Low levels of c-jun transcripts were detectable in untreated HL-60 leukemic cells, increased significantly by 6 h, and reached near maximal levels by 24 h of exposure to 32 nM TPA. Similar kinetics of c-jun induction by TPA were observed in human U-937 and THP-1 monocytic leukemia cells. Similar findings were obtained with bryostatin 1 (10 nM), another activator of protein kinase C and inducer of monocytic differentiation. Furthermore, 1,25-dihydroxyvitamin D3 (0.5 microM), a structurally distinct agent which also induces HL-60 monocytic differentiation, increased c-jun expression. TPA treatment of HL-60 cells in the presence of cycloheximide was associated with superinduction of c-jun transcripts. Run-on analysis demonstrated detectable levels of c-jun gene transcription in untreated HL-60 cells, and that exposure to TPA increases this rate 3.3-fold. Treatment of HL-60 cells with both TPA and cycloheximide had no effect on the rates of c-jun transcription. The half-life of c-jun RNA as determined by treating HL-60 cells with TPA and actinomycin D was 30 min. In contrast, the half-life of c-jun RNA in TPA-treated HL-60 cells exposed to cycloheximide and actinomycin D was greater than 2 h. These findings suggested that the increase in c-jun RNA observed during TPA-induced monocytic differentiation is mediated by both transcriptional and post-transcriptional mechanisms.\n" ], "offsets": [ [ 0, 1885 ] ] } ]

[ { "id": "PMID-2105946_T1", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 55, 60 ] ], "normalized": [] }, { "id": "PMID-2105946_T2", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 172, 177 ] ], "normalized": [] }, { "id": "PMID-2105946_T3", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 423, 428 ] ], "normalized": [] }, { "id": "PMID-2105946_T4", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 508, 513 ] ], "normalized": [] }, { "id": "PMID-2105946_T5", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 695, 700 ] ], "normalized": [] }, { "id": "PMID-2105946_T6", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1065, 1070 ] ], "normalized": [] }, { "id": "PMID-2105946_T7", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1183, 1188 ] ], "normalized": [] }, { "id": "PMID-2105946_T8", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1252, 1257 ] ], "normalized": [] }, { "id": "PMID-2105946_T9", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1445, 1450 ] ], "normalized": [] }, { "id": "PMID-2105946_T10", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1483, 1488 ] ], "normalized": [] }, { "id": "PMID-2105946_T11", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1600, 1605 ] ], "normalized": [] }, { "id": "PMID-2105946_T12", "type": "Protein", "text": [ "c-jun" ], "offsets": [ [ 1748, 1753 ] ], "normalized": [] }, { "id": "PMID-2105946_T13", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 139, 143 ] ], "normalized": [] }, { "id": "PMID-2105946_T14", "type": "Entity", "text": [ "specific DNA sequences" ], "offsets": [ [ 203, 225 ] ], "normalized": [] }, { "id": "PMID-2105946_T15", "type": "Entity", "text": [ "genes" ], "offsets": [ [ 258, 263 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-2105946_R1", "type": "Subunit-Complex", "arg1_id": "PMID-2105946_T2", "arg2_id": "PMID-2105946_T13", "normalized": [] } ]

[ { "id": "PMID-1907460__text", "type": "abstract", "text": [ "Inhibition of HIV-1 replication and NF-kappa B activity by cysteine and cysteine derivatives. \nHIV-1 proviral DNA contains two binding sites for the transcription factor NF-kappa B. HIV-1-infected individuals have, on average, abnormally high levels of tumour necrosis factor alpha (TNF alpha) and abnormally low plasma cysteine levels. We therefore investigated the effects of cysteine and related thiols on HIV-1 replication and NF-kappa B expression. The experiments in this report show that cysteine or N-acetylcysteine (NAC) raise the intracellular glutathione (GSH) level and inhibit HIV-1 replication in persistently infected Molt-4 and U937 cells. However, inhibition of HIV-1 replication appears not to be directly correlated with GSH levels. Cysteine and NAC also inhibit NF-kappa B activity as determined by electrophoretic mobility shift assays and chloramphenicol acetyl-transferase (CAT) gene expression under control of NF-kappa B binding sites in uninfected cells. This suggests that the cysteine deficiency in HIV-1-infected individuals may cause an over-expression of NF-kappa B-dependent genes and enhance HIV-1 replication. NAC may be considered for the treatment of HIV-1-infected individuals.\n" ], "offsets": [ [ 0, 1215 ] ] } ]

[ { "id": "PMID-1907460_T1", "type": "Protein", "text": [ "tumour necrosis factor alpha" ], "offsets": [ [ 253, 281 ] ], "normalized": [] }, { "id": "PMID-1907460_T2", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 283, 292 ] ], "normalized": [] }, { "id": "PMID-1907460_T3", "type": "Protein", "text": [ "chloramphenicol acetyl-transferase" ], "offsets": [ [ 861, 895 ] ], "normalized": [] }, { "id": "PMID-1907460_T4", "type": "Protein", "text": [ "CAT" ], "offsets": [ [ 897, 900 ] ], "normalized": [] }, { "id": "PMID-1907460_T5", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 36, 46 ] ], "normalized": [] }, { "id": "PMID-1907460_T6", "type": "Entity", "text": [ "cysteine" ], "offsets": [ [ 59, 67 ] ], "normalized": [] }, { "id": "PMID-1907460_T7", "type": "Entity", "text": [ "binding sites" ], "offsets": [ [ 127, 140 ] ], "normalized": [] }, { "id": "PMID-1907460_T8", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 170, 180 ] ], "normalized": [] }, { "id": "PMID-1907460_T9", "type": "Entity", "text": [ "cysteine" ], "offsets": [ [ 320, 328 ] ], "normalized": [] }, { "id": "PMID-1907460_T10", "type": "Entity", "text": [ "cysteine" ], "offsets": [ [ 378, 386 ] ], "normalized": [] }, { "id": "PMID-1907460_T11", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 431, 441 ] ], "normalized": [] }, { "id": "PMID-1907460_T12", "type": "Entity", "text": [ "cysteine" ], "offsets": [ [ 495, 503 ] ], "normalized": [] }, { "id": "PMID-1907460_T13", "type": "Entity", "text": [ "N-acetylcysteine" ], "offsets": [ [ 507, 523 ] ], "normalized": [] }, { "id": "PMID-1907460_T14", "type": "Entity", "text": [ "NAC" ], "offsets": [ [ 525, 528 ] ], "normalized": [] }, { "id": "PMID-1907460_T15", "type": "Entity", "text": [ "glutathione" ], "offsets": [ [ 554, 565 ] ], "normalized": [] }, { "id": "PMID-1907460_T16", "type": "Entity", "text": [ "GSH" ], "offsets": [ [ 567, 570 ] ], "normalized": [] }, { "id": "PMID-1907460_T17", "type": "Entity", "text": [ "GSH" ], "offsets": [ [ 740, 743 ] ], "normalized": [] }, { "id": "PMID-1907460_T18", "type": "Entity", "text": [ "Cysteine" ], "offsets": [ [ 752, 760 ] ], "normalized": [] }, { "id": "PMID-1907460_T19", "type": "Entity", "text": [ "NAC" ], "offsets": [ [ 765, 768 ] ], "normalized": [] }, { "id": "PMID-1907460_T20", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 782, 792 ] ], "normalized": [] }, { "id": "PMID-1907460_T21", "type": "Entity", "text": [ "NF-kappa B binding sites" ], "offsets": [ [ 935, 959 ] ], "normalized": [] }, { "id": "PMID-1907460_T22", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 935, 945 ] ], "normalized": [] }, { "id": "PMID-1907460_T23", "type": "Entity", "text": [ "cysteine" ], "offsets": [ [ 1004, 1012 ] ], "normalized": [] }, { "id": "PMID-1907460_T24", "type": "Entity", "text": [ "NF-kappa B-dependent genes" ], "offsets": [ [ 1086, 1112 ] ], "normalized": [] }, { "id": "PMID-1907460_T25", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1086, 1096 ] ], "normalized": [] }, { "id": "PMID-1907460_T26", "type": "Entity", "text": [ "NAC" ], "offsets": [ [ 1144, 1147 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-1907460_1", "entity_ids": [ "PMID-1907460_T1", "PMID-1907460_T2" ] }, { "id": "PMID-1907460_2", "entity_ids": [ "PMID-1907460_T3", "PMID-1907460_T4" ] } ]

[]

[ { "id": "PMID-9032265__text", "type": "abstract", "text": [ "Transcriptional regulation of the ferritin heavy-chain gene: the activity of the CCAAT binding factor NF-Y is modulated in heme-treated Friend leukemia cells and during monocyte-to-macrophage differentiation. \nThe ferritin H-chain gene promoter regulation was analyzed in heme-treated Friend leukemia cells (FLCs) and during monocyte-to-macrophage differentiation. In the majority of cell lines studied, the regulation of ferritin expression was exerted mostly at the translational level. However, in differentiating erythroid cells, which must incorporate high levels of iron to sustain hemoglobin synthesis, and in macrophages, which are involved in iron storage, transcriptional regulation seemed to be a relevant mechanism. We show here that the minimum region of the ferritin H-gene promoter that is able to confer transcriptional regulation by heme in FLCs to a reporter gene is 77 nucleotides upstream of the TATA box. This cis element binds a protein complex referred to as HRF (heme-responsive factor), which is greatly enhanced both in heme-treated FLCs and during monocyte-to-macrophage differentiation. The CCAAT element present in reverse orientation in this promoter region of the ferritin H-chain gene is necessary for binding and for gene activity, since a single point mutation is able to abolish the binding of HRF and the transcriptional activity in transfected cells. By competition experiments and supershift assays, we identified the induced HRF as containing at least the ubiquitous transcription factor NF-Y. NF-Y is formed by three subunits, A, B, and C, all of which are necessary for DNA binding. Cotransfection with a transdominant negative mutant of the NF-YA subunit abolishes the transcriptional activation by heme, indicating that NF-Y plays an essential role in this activation. We have also observed a differential expression of the NF-YA subunit in heme-treated and control FLCs and during monocyte-to-macrophage differentiation.\n" ], "offsets": [ [ 0, 1965 ] ] } ]

[ { "id": "PMID-9032265_T1", "type": "Protein", "text": [ "ferritin H-chain" ], "offsets": [ [ 214, 230 ] ], "normalized": [] }, { "id": "PMID-9032265_T2", "type": "Protein", "text": [ "ferritin H" ], "offsets": [ [ 772, 782 ] ], "normalized": [] }, { "id": "PMID-9032265_T3", "type": "Protein", "text": [ "ferritin H-chain" ], "offsets": [ [ 1195, 1211 ] ], "normalized": [] }, { "id": "PMID-9032265_T4", "type": "Entity", "text": [ "ferritin heavy-chain gene" ], "offsets": [ [ 34, 59 ] ], "normalized": [] }, { "id": "PMID-9032265_T5", "type": "Entity", "text": [ "CCAAT binding factor NF-Y" ], "offsets": [ [ 81, 106 ] ], "normalized": [] }, { "id": "PMID-9032265_T6", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 236, 244 ] ], "normalized": [] }, { "id": "PMID-9032265_T7", "type": "Entity", "text": [ "hemoglobin" ], "offsets": [ [ 588, 598 ] ], "normalized": [] }, { "id": "PMID-9032265_T8", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 788, 796 ] ], "normalized": [] }, { "id": "PMID-9032265_T9", "type": "Entity", "text": [ "reporter gene" ], "offsets": [ [ 868, 881 ] ], "normalized": [] }, { "id": "PMID-9032265_T10", "type": "Entity", "text": [ "77 nucleotides upstream of the TATA box." ], "offsets": [ [ 885, 925 ] ], "normalized": [] }, { "id": "PMID-9032265_T11", "type": "Entity", "text": [ "77 nucleotides upstream" ], "offsets": [ [ 885, 908 ] ], "normalized": [] }, { "id": "PMID-9032265_T12", "type": "Entity", "text": [ "TATA box" ], "offsets": [ [ 916, 924 ] ], "normalized": [] }, { "id": "PMID-9032265_T13", "type": "Entity", "text": [ "cis element" ], "offsets": [ [ 931, 942 ] ], "normalized": [] }, { "id": "PMID-9032265_T14", "type": "Entity", "text": [ "HRF" ], "offsets": [ [ 982, 985 ] ], "normalized": [] }, { "id": "PMID-9032265_T15", "type": "Entity", "text": [ "heme-responsive factor" ], "offsets": [ [ 987, 1009 ] ], "normalized": [] }, { "id": "PMID-9032265_T16", "type": "Entity", "text": [ "CCAAT element" ], "offsets": [ [ 1119, 1132 ] ], "normalized": [] }, { "id": "PMID-9032265_T17", "type": "Entity", "text": [ "HRF" ], "offsets": [ [ 1329, 1332 ] ], "normalized": [] }, { "id": "PMID-9032265_T18", "type": "Entity", "text": [ "HRF" ], "offsets": [ [ 1464, 1467 ] ], "normalized": [] }, { "id": "PMID-9032265_T19", "type": "Entity", "text": [ "NF-Y" ], "offsets": [ [ 1533, 1537 ] ], "normalized": [] }, { "id": "PMID-9032265_T20", "type": "Entity", "text": [ "NF-Y" ], "offsets": [ [ 1763, 1767 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-9032265_R1", "type": "Protein-Component", "arg1_id": "PMID-9032265_T1", "arg2_id": "PMID-9032265_T6", "normalized": [] }, { "id": "PMID-9032265_R2", "type": "Protein-Component", "arg1_id": "PMID-9032265_T2", "arg2_id": "PMID-9032265_T10", "normalized": [] }, { "id": "PMID-9032265_R3", "type": "Protein-Component", "arg1_id": "PMID-9032265_T2", "arg2_id": "PMID-9032265_T11", "normalized": [] }, { "id": "PMID-9032265_R4", "type": "Protein-Component", "arg1_id": "PMID-9032265_T2", "arg2_id": "PMID-9032265_T12", "normalized": [] }, { "id": "PMID-9032265_R5", "type": "Protein-Component", "arg1_id": "PMID-9032265_T2", "arg2_id": "PMID-9032265_T8", "normalized": [] }, { "id": "PMID-9032265_R6", "type": "Protein-Component", "arg1_id": "PMID-9032265_T3", "arg2_id": "PMID-9032265_T16", "normalized": [] } ]

[ { "id": "PMID-9837745__text", "type": "abstract", "text": [ "Interleukin-12 expression in B cells by transformation with Epstein-Barr virus. \nAlthough interleukin (IL)-12 was originally purified from an Epstein-Barr (EBV)-transformed B cell line and the high correlation of EBV infection and IL-12 expression has been suggested, no study has reported whether EBV infection is directly linked to IL-12 expression. To address this issue, we have investigated IL-12 expression in B cells during in vitro transformation with EBV. Human peripheral B cells became capable of constitutively producing p40 by in vitro transformation with EBV, coincident with the expression of latent membrane protein 1 (LMP1) of EBV. These B cells expressed p40 and p35 mRNA, and phorbol myristate acetate (PMA) stimulation strongly enhanced p40 and p70 production. Furthermore, transfection with LMP1 expression vector into a human B lymphoma cell line, Daudi, led to p40 production with nuclear factor (NF)-kappaB activation. These results suggest that transformation of primary B cells with EBV induces IL-12 expression potentially through LMP1 expression. Copyright 1998 Academic Press.\n" ], "offsets": [ [ 0, 1106 ] ] } ]

[ { "id": "PMID-9837745_T1", "type": "Protein", "text": [ "p40" ], "offsets": [ [ 533, 536 ] ], "normalized": [] }, { "id": "PMID-9837745_T2", "type": "Protein", "text": [ "latent membrane protein 1" ], "offsets": [ [ 608, 633 ] ], "normalized": [] }, { "id": "PMID-9837745_T3", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 635, 639 ] ], "normalized": [] }, { "id": "PMID-9837745_T4", "type": "Protein", "text": [ "p40" ], "offsets": [ [ 673, 676 ] ], "normalized": [] }, { "id": "PMID-9837745_T5", "type": "Protein", "text": [ "p35" ], "offsets": [ [ 681, 684 ] ], "normalized": [] }, { "id": "PMID-9837745_T6", "type": "Protein", "text": [ "p40" ], "offsets": [ [ 757, 760 ] ], "normalized": [] }, { "id": "PMID-9837745_T7", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 812, 816 ] ], "normalized": [] }, { "id": "PMID-9837745_T8", "type": "Protein", "text": [ "p40" ], "offsets": [ [ 884, 887 ] ], "normalized": [] }, { "id": "PMID-9837745_T9", "type": "Protein", "text": [ "LMP1" ], "offsets": [ [ 1058, 1062 ] ], "normalized": [] }, { "id": "PMID-9837745_T10", "type": "Entity", "text": [ "Interleukin-12" ], "offsets": [ [ 0, 14 ] ], "normalized": [] }, { "id": "PMID-9837745_T11", "type": "Entity", "text": [ "interleukin (IL)-12" ], "offsets": [ [ 90, 109 ] ], "normalized": [] }, { "id": "PMID-9837745_T12", "type": "Entity", "text": [ "IL-12" ], "offsets": [ [ 231, 236 ] ], "normalized": [] }, { "id": "PMID-9837745_T13", "type": "Entity", "text": [ "IL-12" ], "offsets": [ [ 334, 339 ] ], "normalized": [] }, { "id": "PMID-9837745_T14", "type": "Entity", "text": [ "IL-12" ], "offsets": [ [ 396, 401 ] ], "normalized": [] }, { "id": "PMID-9837745_T15", "type": "Entity", "text": [ "p70" ], "offsets": [ [ 765, 768 ] ], "normalized": [] }, { "id": "PMID-9837745_T16", "type": "Entity", "text": [ "nuclear factor (NF)-kappaB" ], "offsets": [ [ 904, 930 ] ], "normalized": [] }, { "id": "PMID-9837745_T17", "type": "Entity", "text": [ "IL-12" ], "offsets": [ [ 1021, 1026 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-9837745_1", "entity_ids": [ "PMID-9837745_T2", "PMID-9837745_T3" ] } ]

[]

[ { "id": "PMID-7594468__text", "type": "abstract", "text": [ "Regulation of IkB alpha phosphorylation by PKC- and Ca(2+)-dependent signal transduction pathways. \nThe Ca(2+)-dependent phosphatase calcineurin, a target of FK506 and CsA, synergizes with PKC-induced activation of nuclear factor (NF)-kappa B in T cell lines. We have investigated whether this synergy is present in other cell types and the mechanism(s) by which these two pathways lead to NF-kappa B activation. While this synergy is present in other cell types, in the monocytic cell line U937 calcineurin is also sufficient to activate NF-kappa B. Having previously shown that Ca(2+)- and PKC-dependent pathways synergize by accelerating the degradation of IkB alpha, we focused on the regulation of IkB alpha phosphorylation. While PKC-dependent pathways sequentially result in the phosphorylation and in an incomplete degradation of IkB alpha in T cell lines, co-activation of Ca(2+)-dependent pathways accelerates the rate of IkB alpha phosphorylation and results in its complete degradation. Activation of Ca(2+)-dependent pathways alone do not result in the phosphorylation and/or degradation of IkB alpha in Jurkat T or in U937 cells. Treatment of T cells with the selective PKC inhibitor GF109203X abrogates the PMA-induced IkB alpha phosphorylation/degradation irrespective of activation of Ca(2+)-dependent pathways, but not the phosphorylation and degradation of IkB alpha induced by TNF-alpha, a PKC-independent stimulus. Contrary to the interaction with PKC, Ca(2+)-dependent pathways synergize with TNF-alpha not at the level of IkB alpha phosphorylation, but at the level of its degradation. These results indicate that Ca(2+)-dependent pathways, including the phosphatase calcineurin, participate in the regulation of NF-kappa B in a cell specific fashion and synergize with PKC-dependent and -independent pathways at the level of IkB alpha phosphorylation and degradation.\n" ], "offsets": [ [ 0, 1892 ] ] } ]

[ { "id": "PMID-7594468_T1", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 14, 23 ] ], "normalized": [] }, { "id": "PMID-7594468_T2", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 660, 669 ] ], "normalized": [] }, { "id": "PMID-7594468_T3", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 703, 712 ] ], "normalized": [] }, { "id": "PMID-7594468_T4", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 838, 847 ] ], "normalized": [] }, { "id": "PMID-7594468_T5", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 932, 941 ] ], "normalized": [] }, { "id": "PMID-7594468_T6", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 1104, 1113 ] ], "normalized": [] }, { "id": "PMID-7594468_T7", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 1234, 1243 ] ], "normalized": [] }, { "id": "PMID-7594468_T8", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 1376, 1385 ] ], "normalized": [] }, { "id": "PMID-7594468_T9", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1397, 1406 ] ], "normalized": [] }, { "id": "PMID-7594468_T10", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1515, 1524 ] ], "normalized": [] }, { "id": "PMID-7594468_T11", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 1545, 1554 ] ], "normalized": [] }, { "id": "PMID-7594468_T12", "type": "Protein", "text": [ "IkB alpha" ], "offsets": [ [ 1849, 1858 ] ], "normalized": [] }, { "id": "PMID-7594468_T13", "type": "Entity", "text": [ "calcineurin" ], "offsets": [ [ 133, 144 ] ], "normalized": [] }, { "id": "PMID-7594468_T14", "type": "Entity", "text": [ "nuclear factor (NF)-kappa B" ], "offsets": [ [ 215, 242 ] ], "normalized": [] }, { "id": "PMID-7594468_T15", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 390, 400 ] ], "normalized": [] }, { "id": "PMID-7594468_T16", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 539, 549 ] ], "normalized": [] }, { "id": "PMID-7594468_T17", "type": "Entity", "text": [ "calcineurin" ], "offsets": [ [ 1690, 1701 ] ], "normalized": [] }, { "id": "PMID-7594468_T18", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1736, 1746 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-10202024__text", "type": "abstract", "text": [ "Human cytomegalovirus binding to human monocytes induces immunoregulatory gene expression. \nTo continue our investigation of the cellular events that occur following human CMV (HCMV) infection, we focused on the regulation of cellular activation following viral binding to human monocytes. First, we showed that viral binding induced a number of immunoregulatory genes (IL-1beta, A20, NF-kappaB-p105/p50, and IkappaBalpha) in unactivated monocytes and that neutralizing Abs to the major HCMV glycoproteins, gB (UL55) and gH (UL75), inhibited the induction of these genes. Next, we demonstrated that these viral ligands directly up-regulated monocyte gene expression upon their binding to their appropriate cellular receptors. We then investigated if HCMV binding also resulted in the translation and secretion of cytokines. Our results showed that HCMV binding to monocytes resulted in the production and release of IL-1beta protein. Because these induced gene products have NF-kappaB sites in their promoter regions, we next examined whether there was an up-regulation of nuclear NF-kappaB levels. These experiments showed that, in fact, NF-kappaB was translocated to the nucleus following viral binding or purified viral ligand binding. Changes in IkappaBalpha levels correlated with the changes in NF-kappaB translocation. Lastly, we demonstrated that p38 kinase activity played a central role in IL-1beta production and that it was rapidly up-regulated following infection. These results support our hypothesis that HCMV initiates a signal transduction pathway that leads to monocyte activation and pinpoints a potential mechanism whereby HCMV infection of monocytes can result in profound pathogenesis, especially in chronic inflammatory-type conditions.\n" ], "offsets": [ [ 0, 1760 ] ] } ]

[ { "id": "PMID-10202024_T1", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 370, 378 ] ], "normalized": [] }, { "id": "PMID-10202024_T2", "type": "Protein", "text": [ "A20" ], "offsets": [ [ 380, 383 ] ], "normalized": [] }, { "id": "PMID-10202024_T3", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 395, 399 ] ], "normalized": [] }, { "id": "PMID-10202024_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 400, 403 ] ], "normalized": [] }, { "id": "PMID-10202024_T5", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 409, 421 ] ], "normalized": [] }, { "id": "PMID-10202024_T6", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 916, 924 ] ], "normalized": [] }, { "id": "PMID-10202024_T7", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 1250, 1262 ] ], "normalized": [] }, { "id": "PMID-10202024_T8", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 1400, 1408 ] ], "normalized": [] }, { "id": "PMID-10202024_T9", "type": "Entity", "text": [ "immunoregulatory gene" ], "offsets": [ [ 57, 78 ] ], "normalized": [] }, { "id": "PMID-10202024_T10", "type": "Entity", "text": [ "immunoregulatory genes" ], "offsets": [ [ 346, 368 ] ], "normalized": [] }, { "id": "PMID-10202024_T11", "type": "Entity", "text": [ "NF-kappaB-p105/p50" ], "offsets": [ [ 385, 403 ] ], "normalized": [] }, { "id": "PMID-10202024_T12", "type": "Entity", "text": [ "NF-kappaB sites" ], "offsets": [ [ 975, 990 ] ], "normalized": [] }, { "id": "PMID-10202024_T13", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 975, 984 ] ], "normalized": [] }, { "id": "PMID-10202024_T14", "type": "Entity", "text": [ "promoter regions" ], "offsets": [ [ 1000, 1016 ] ], "normalized": [] }, { "id": "PMID-10202024_T15", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1081, 1090 ] ], "normalized": [] }, { "id": "PMID-10202024_T16", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1139, 1148 ] ], "normalized": [] }, { "id": "PMID-10202024_T17", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1301, 1310 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-10202024_R1", "type": "Subunit-Complex", "arg1_id": "PMID-10202024_T3", "arg2_id": "PMID-10202024_T11", "normalized": [] }, { "id": "PMID-10202024_R2", "type": "Subunit-Complex", "arg1_id": "PMID-10202024_T4", "arg2_id": "PMID-10202024_T11", "normalized": [] } ]

[ { "id": "PMID-8573121__text", "type": "abstract", "text": [ "Inhibition of NF-kappa B activation in human T-cell lines by anetholdithiolthione. \nNuclear factor (NF)-kappa B is a redox sensitive cytosolic transcription factor. Redox regulation of NF-kappa B has been implicated in the activation of the human immuno-deficiency virus (HIV). Therefore, inhibition of NF-kappa B activation may be an effective strategy for acquired immunodeficiency syndrome therapy. Anetholdithiolthione (ADT, 5-[p-methoxyphenyl]-3H-1,2-dithiol-3-thione) is an antioxidant which has been used to protect against acetaminophen- and CCl4-induced hepatotoxicity, lipid peroxidation, radiation injury, and also has been used clinically as an anti-choleretic agent. The present study examined the effect of ADT pretreatment on NF-kappa B activation in response to a variety of stimuli such as H2O2, phorbol myristate acetate (PMA) or tumor necrosis factor alpha (TNF alpha). PMA and TNF alpha induced activation of (NF)-kappa B in human Jurkat T-cells was partially inhibited by ADT (0.1 mM) pretreatment. ADT (0.1 mM) also inhibited H2O2 induced activation of the transcription factor in the peroxide sensitive human Wurzburg T-cells. Furthermore, ADT treated Wurzburg cells had significantly higher glutathione levels as compared with untreated cells. H2O2 induced lipid peroxidation in Wurzburg cells was remarkably inhibited by ADT pretreatment. ADT, a pro-glutathione antioxidant, was observed to be capable of modulating NF-kappa B activation.\n" ], "offsets": [ [ 0, 1464 ] ] } ]

[ { "id": "PMID-8573121_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 848, 875 ] ], "normalized": [] }, { "id": "PMID-8573121_T2", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 877, 886 ] ], "normalized": [] }, { "id": "PMID-8573121_T3", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 897, 906 ] ], "normalized": [] }, { "id": "PMID-8573121_T4", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 14, 24 ] ], "normalized": [] }, { "id": "PMID-8573121_T5", "type": "Entity", "text": [ "Nuclear factor (NF)-kappa B" ], "offsets": [ [ 84, 111 ] ], "normalized": [] }, { "id": "PMID-8573121_T6", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 185, 195 ] ], "normalized": [] }, { "id": "PMID-8573121_T7", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 303, 313 ] ], "normalized": [] }, { "id": "PMID-8573121_T8", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 741, 751 ] ], "normalized": [] }, { "id": "PMID-8573121_T9", "type": "Entity", "text": [ "(NF)-kappa B" ], "offsets": [ [ 929, 941 ] ], "normalized": [] }, { "id": "PMID-8573121_T10", "type": "Entity", "text": [ "glutathione" ], "offsets": [ [ 1215, 1226 ] ], "normalized": [] }, { "id": "PMID-8573121_T11", "type": "Entity", "text": [ "glutathione" ], "offsets": [ [ 1375, 1386 ] ], "normalized": [] }, { "id": "PMID-8573121_T12", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1441, 1451 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-8573121_1", "entity_ids": [ "PMID-8573121_T1", "PMID-8573121_T2" ] } ]

[]

[ { "id": "PMID-10229841__text", "type": "abstract", "text": [ "Signaling through the lymphotoxin-beta receptor stimulates HIV-1 replication alone and in cooperation with soluble or membrane-bound TNF-alpha. \nThe level of ongoing HIV-1 replication within an individual is critical to HIV-1 pathogenesis. Among host immune factors, the cytokine TNF-alpha has previously been shown to increase HIV-1 replication in various monocyte and T cell model systems. Here, we demonstrate that signaling through the TNF receptor family member, the lymphotoxin-beta (LT-beta) receptor (LT-betaR), also regulates HIV-1 replication. Furthermore, HIV-1 replication is cooperatively stimulated when the distinct LT-betaR and TNF receptor systems are simultaneously engaged by their specific ligands. Moreover, in a physiological coculture cellular assay system, we show that membrane-bound TNF-alpha and LT-alpha1beta2 act virtually identically to their soluble forms in the regulation of HIV-1 replication. Thus, cosignaling via the LT-beta and TNF-alpha receptors is probably involved in the modulation of HIV-1 replication and the subsequent determination of HIV-1 viral burden in monocytes. Intriguingly, surface expression of LT-alpha1beta2 is up-regulated on a T cell line acutely infected with HIV-1, suggesting a positive feedback loop between HIV-1 infection, LT-alpha1beta2 expression, and HIV-1 replication. Given the critical role that LT-alpha1beta2 plays in lymphoid architecture, we speculate that LT-alpha1beta2 may be involved in HIV-associated abnormalities of the lymphoid organs.\n" ], "offsets": [ [ 0, 1519 ] ] } ]

[ { "id": "PMID-10229841_T1", "type": "Protein", "text": [ "lymphotoxin-beta receptor" ], "offsets": [ [ 22, 47 ] ], "normalized": [] }, { "id": "PMID-10229841_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 133, 142 ] ], "normalized": [] }, { "id": "PMID-10229841_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 280, 289 ] ], "normalized": [] }, { "id": "PMID-10229841_T4", "type": "Protein", "text": [ "lymphotoxin-beta (LT-beta) receptor" ], "offsets": [ [ 472, 507 ] ], "normalized": [] }, { "id": "PMID-10229841_T5", "type": "Protein", "text": [ "LT-betaR" ], "offsets": [ [ 509, 517 ] ], "normalized": [] }, { "id": "PMID-10229841_T6", "type": "Protein", "text": [ "LT-betaR" ], "offsets": [ [ 631, 639 ] ], "normalized": [] }, { "id": "PMID-10229841_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 809, 818 ] ], "normalized": [] }, { "id": "PMID-10229841_T8", "type": "Protein", "text": [ "LT-beta" ], "offsets": [ [ 953, 960 ] ], "normalized": [] }, { "id": "PMID-10229841_T9", "type": "Protein", "text": [ "TNF-alpha receptors" ], "offsets": [ [ 965, 984 ] ], "normalized": [] }, { "id": "PMID-10229841_T10", "type": "Entity", "text": [ "LT-alpha1beta2" ], "offsets": [ [ 823, 837 ] ], "normalized": [] }, { "id": "PMID-10229841_T11", "type": "Entity", "text": [ "LT-alpha1beta2" ], "offsets": [ [ 1150, 1164 ] ], "normalized": [] }, { "id": "PMID-10229841_T12", "type": "Entity", "text": [ "LT-alpha1beta2" ], "offsets": [ [ 1288, 1302 ] ], "normalized": [] }, { "id": "PMID-10229841_T13", "type": "Entity", "text": [ "LT-alpha1beta2" ], "offsets": [ [ 1367, 1381 ] ], "normalized": [] }, { "id": "PMID-10229841_T14", "type": "Entity", "text": [ "LT-alpha1beta2" ], "offsets": [ [ 1432, 1446 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-10229841_1", "entity_ids": [ "PMID-10229841_T4", "PMID-10229841_T5" ] } ]

[]

[ { "id": "PMID-7843230__text", "type": "abstract", "text": [ "Biphasic control of nuclear factor-kappa B activation by the T cell receptor complex: role of tumor necrosis factor alpha. \nThe regulation of nuclear factor (NF)-kappa B activation by the T cell receptor (TcR)/CD3 complex in primary human T cells has been studied at various times after activation. Only p50 NF-kappa B protein bound the kappa B element of interleukin-2 receptor (IL-2R) alpha chain promoter on resting T cells. However, immediately after TcR/CD3 cross-linking (after approximately 1 h; immediate) binding of p50.p65 heterodimers was observed. p50.c-rel heterodimers were also detected bound to this sequence at early time points (7-16 h; early), and both remained active at later time points (40 h; late) after activation. This regulation takes place mainly at the level of nuclear translocation of p65 and c-rel, at immediate and early time points. Activation also induced c-rel and p105/p50 mRNA synthesis, but not p65 mRNA whose expression was constitutive. Interestingly, all those early and late events, but not the immediate ones, were inhibited by a neutralizing anti-tumor necrosis factor alpha (TNF-alpha) monoclonal antibody. Similarly, cycloheximide prevented the p65 and c-rel translocation and consequent formation of active binding heterodimers, at early and late times. Cyclosporin A impaired not only early and late, but also immediate events; however, addition of TNF-alpha prevented all inhibition. These results indicate that the regulation of NF-kappa B activation during T cell activation by TcR/CD3 signals is biphasic: TcR/CD3 triggers its immediate translocation, which is transient if no TNF-alpha is present. TNF-alpha, therefore, emerges as the main factor responsible for a second phase of NF-kappa B regulation, controlling both translocation of p65 and c-rel, and new mRNA synthesis for c-rel and p105/p50.\n" ], "offsets": [ [ 0, 1854 ] ] } ]

[ { "id": "PMID-7843230_T1", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 94, 121 ] ], "normalized": [] }, { "id": "PMID-7843230_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 304, 307 ] ], "normalized": [] }, { "id": "PMID-7843230_T3", "type": "Protein", "text": [ "interleukin-2 receptor (IL-2R) alpha chain" ], "offsets": [ [ 356, 398 ] ], "normalized": [] }, { "id": "PMID-7843230_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 525, 528 ] ], "normalized": [] }, { "id": "PMID-7843230_T5", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 529, 532 ] ], "normalized": [] }, { "id": "PMID-7843230_T6", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 560, 563 ] ], "normalized": [] }, { "id": "PMID-7843230_T7", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 564, 569 ] ], "normalized": [] }, { "id": "PMID-7843230_T8", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 816, 819 ] ], "normalized": [] }, { "id": "PMID-7843230_T9", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 824, 829 ] ], "normalized": [] }, { "id": "PMID-7843230_T10", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 891, 896 ] ], "normalized": [] }, { "id": "PMID-7843230_T11", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 901, 905 ] ], "normalized": [] }, { "id": "PMID-7843230_T12", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 906, 909 ] ], "normalized": [] }, { "id": "PMID-7843230_T13", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 934, 937 ] ], "normalized": [] }, { "id": "PMID-7843230_T14", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 1092, 1119 ] ], "normalized": [] }, { "id": "PMID-7843230_T15", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1121, 1130 ] ], "normalized": [] }, { "id": "PMID-7843230_T16", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1192, 1195 ] ], "normalized": [] }, { "id": "PMID-7843230_T17", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 1200, 1205 ] ], "normalized": [] }, { "id": "PMID-7843230_T18", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1398, 1407 ] ], "normalized": [] }, { "id": "PMID-7843230_T19", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1630, 1639 ] ], "normalized": [] }, { "id": "PMID-7843230_T20", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1652, 1661 ] ], "normalized": [] }, { "id": "PMID-7843230_T21", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1792, 1795 ] ], "normalized": [] }, { "id": "PMID-7843230_T22", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 1800, 1805 ] ], "normalized": [] }, { "id": "PMID-7843230_T23", "type": "Protein", "text": [ "c-rel" ], "offsets": [ [ 1834, 1839 ] ], "normalized": [] }, { "id": "PMID-7843230_T24", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 1844, 1848 ] ], "normalized": [] }, { "id": "PMID-7843230_T25", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1849, 1852 ] ], "normalized": [] }, { "id": "PMID-7843230_T26", "type": "Entity", "text": [ "nuclear factor-kappa B" ], "offsets": [ [ 20, 42 ] ], "normalized": [] }, { "id": "PMID-7843230_T27", "type": "Entity", "text": [ "T cell receptor complex" ], "offsets": [ [ 61, 84 ] ], "normalized": [] }, { "id": "PMID-7843230_T28", "type": "Entity", "text": [ "nuclear factor (NF)-kappa B" ], "offsets": [ [ 142, 169 ] ], "normalized": [] }, { "id": "PMID-7843230_T29", "type": "Entity", "text": [ "T cell receptor (TcR)/CD3 complex" ], "offsets": [ [ 188, 221 ] ], "normalized": [] }, { "id": "PMID-7843230_T30", "type": "Entity", "text": [ "kappa B element of interleukin-2 receptor (IL-2R) alpha chain promoter" ], "offsets": [ [ 337, 407 ] ], "normalized": [] }, { "id": "PMID-7843230_T31", "type": "Entity", "text": [ "kappa B element" ], "offsets": [ [ 337, 352 ] ], "normalized": [] }, { "id": "PMID-7843230_T32", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 399, 407 ] ], "normalized": [] }, { "id": "PMID-7843230_T33", "type": "Entity", "text": [ "TcR" ], "offsets": [ [ 455, 458 ] ], "normalized": [] }, { "id": "PMID-7843230_T34", "type": "Entity", "text": [ "CD3" ], "offsets": [ [ 459, 462 ] ], "normalized": [] }, { "id": "PMID-7843230_T35", "type": "Entity", "text": [ "heterodimers" ], "offsets": [ [ 533, 545 ] ], "normalized": [] }, { "id": "PMID-7843230_T36", "type": "Entity", "text": [ "heterodimers" ], "offsets": [ [ 570, 582 ] ], "normalized": [] }, { "id": "PMID-7843230_T37", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1480, 1490 ] ], "normalized": [] }, { "id": "PMID-7843230_T38", "type": "Entity", "text": [ "TcR/CD3" ], "offsets": [ [ 1530, 1537 ] ], "normalized": [] }, { "id": "PMID-7843230_T39", "type": "Entity", "text": [ "TcR/CD3" ], "offsets": [ [ 1559, 1566 ] ], "normalized": [] }, { "id": "PMID-7843230_T40", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1735, 1745 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-7843230_1", "entity_ids": [ "PMID-7843230_T14", "PMID-7843230_T15" ] } ]

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[ { "id": "PMID-8015553__text", "type": "abstract", "text": [ "Nonpituitary human prolactin gene transcription is independent of Pit-1 and differentially controlled in lymphocytes and in endometrial stroma. \nExpression of the human PRL (hPRL) gene in extrapituitary sites such as the uterus (decidualized endometrial stroma and myometrium) and cells of the hematopoietic lineage is directed by an alternative promoter which is located approximately 6 kilobases (kb) upstream of the pituitary-specific start site. In order to delineate the tissue-specific mechanisms governing the control of nonpituitary PRL gene expression, we have cloned and sequenced 3 kb 5'-flanking DNA of the upstream decidual/lymphoid (dPRL) promoter. Based on sequence homology we identified two binding motifs for Pit-1 and seven half-sites for glucocorticoid receptor/progesterone receptor (PR) binding. We focused our studies on the role of Pit-1 and of PR as potential transcriptional regulators, since the POU domain protein Pit-1 is essential in the control of pituitary PRL expression, and progesterone induces decidual transformation of the endometrial stroma, a differentiation process during which the decidual PRL gene is activated. We demonstrate in a variety of cell types, including lymphocytes and endometrial stroma, that Pit-1 is not involved in the regulation of dPRL promoter/reporter gene constructs carrying 3 kb 5'-flanking DNA. Our experiments also show that activated PR does not confer direct transcriptional control on the dPRL promoter. When we compared the activity of the transfected dPRL promoter in PRL-secreting and nonsecreting lymphoid cells, we found that the 3 kb 5'-flanking region of the dPRL promoter did not contain elements restricting expression to only those lymphocytes that produce PRL but allowed expression of fusion reporter genes irrespective of the status of the endogenous PRL gene. This was in sharp contrast to endometrial cells where 3 kb 5'-flanking DNA conferred strong transcriptional activation on the dPRL promoter in decidualized endometrial stromal cells actively secreting PRL, but did not allow transcription in undifferentiated non-PRL-secreting endometrial stromal cells. Activation of the dPRL promoter construct in these undifferentiated cells could however be induced by the addition of cAMP, in the absence of progesterone, suggesting that a signal transduced through the cAMP signaling pathway is a primary inducer of decidual PRL gene expression.\n" ], "offsets": [ [ 0, 2430 ] ] } ]

[ { "id": "PMID-8015553_T1", "type": "Protein", "text": [ "prolactin" ], "offsets": [ [ 19, 28 ] ], "normalized": [] }, { "id": "PMID-8015553_T2", "type": "Protein", "text": [ "Pit-1" ], "offsets": [ [ 66, 71 ] ], "normalized": [] }, { "id": "PMID-8015553_T3", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 169, 172 ] ], "normalized": [] }, { "id": "PMID-8015553_T4", "type": "Protein", "text": [ "hPRL" ], "offsets": [ [ 174, 178 ] ], "normalized": [] }, { "id": "PMID-8015553_T5", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 541, 544 ] ], "normalized": [] }, { "id": "PMID-8015553_T6", "type": "Protein", "text": [ "dPRL" ], "offsets": [ [ 647, 651 ] ], "normalized": [] }, { "id": "PMID-8015553_T7", "type": "Protein", "text": [ "Pit-1" ], "offsets": [ [ 727, 732 ] ], "normalized": [] }, { "id": "PMID-8015553_T8", "type": "Protein", "text": [ "glucocorticoid receptor" ], "offsets": [ [ 758, 781 ] ], "normalized": [] }, { "id": "PMID-8015553_T9", "type": "Protein", "text": [ "progesterone receptor" ], "offsets": [ [ 782, 803 ] ], "normalized": [] }, { "id": "PMID-8015553_T10", "type": "Protein", "text": [ "PR" ], "offsets": [ [ 805, 807 ] ], "normalized": [] }, { "id": "PMID-8015553_T11", "type": "Protein", "text": [ "Pit-1" ], "offsets": [ [ 856, 861 ] ], "normalized": [] }, { "id": "PMID-8015553_T12", "type": "Protein", "text": [ "PR" ], "offsets": [ [ 869, 871 ] ], "normalized": [] }, { "id": "PMID-8015553_T13", "type": "Protein", "text": [ "Pit-1" ], "offsets": [ [ 942, 947 ] ], "normalized": [] }, { "id": "PMID-8015553_T14", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 989, 992 ] ], "normalized": [] }, { "id": "PMID-8015553_T15", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1133, 1136 ] ], "normalized": [] }, { "id": "PMID-8015553_T16", "type": "Protein", "text": [ "Pit-1" ], "offsets": [ [ 1250, 1255 ] ], "normalized": [] }, { "id": "PMID-8015553_T17", "type": "Protein", "text": [ "dPRL" ], "offsets": [ [ 1293, 1297 ] ], "normalized": [] }, { "id": "PMID-8015553_T18", "type": "Protein", "text": [ "PR" ], "offsets": [ [ 1404, 1406 ] ], "normalized": [] }, { "id": "PMID-8015553_T19", "type": "Protein", "text": [ "dPRL" ], "offsets": [ [ 1461, 1465 ] ], "normalized": [] }, { "id": "PMID-8015553_T20", "type": "Protein", "text": [ "dPRL" ], "offsets": [ [ 1525, 1529 ] ], "normalized": [] }, { "id": "PMID-8015553_T21", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1542, 1545 ] ], "normalized": [] }, { "id": "PMID-8015553_T22", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1739, 1742 ] ], "normalized": [] }, { "id": "PMID-8015553_T23", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 1836, 1839 ] ], "normalized": [] }, { "id": "PMID-8015553_T24", "type": "Protein", "text": [ "dPRL" ], "offsets": [ [ 1972, 1976 ] ], "normalized": [] }, { "id": "PMID-8015553_T25", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 2047, 2050 ] ], "normalized": [] }, { "id": "PMID-8015553_T26", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 2108, 2111 ] ], "normalized": [] }, { "id": "PMID-8015553_T27", "type": "Protein", "text": [ "dPRL" ], "offsets": [ [ 2167, 2171 ] ], "normalized": [] }, { "id": "PMID-8015553_T28", "type": "Protein", "text": [ "PRL" ], "offsets": [ [ 2409, 2412 ] ], "normalized": [] }, { "id": "PMID-8015553_T29", "type": "Entity", "text": [ "alternative promoter" ], "offsets": [ [ 334, 354 ] ], "normalized": [] }, { "id": "PMID-8015553_T30", "type": "Entity", "text": [ "6 kilobases (kb) upstream" ], "offsets": [ [ 386, 411 ] ], "normalized": [] }, { "id": "PMID-8015553_T31", "type": "Entity", "text": [ "pituitary-specific start site" ], "offsets": [ [ 419, 448 ] ], "normalized": [] }, { "id": "PMID-8015553_T32", "type": "Entity", "text": [ "3 kb 5'-flanking DNA" ], "offsets": [ [ 591, 611 ] ], "normalized": [] }, { "id": "PMID-8015553_T33", "type": "Entity", "text": [ ") promoter" ], "offsets": [ [ 651, 661 ] ], "normalized": [] }, { "id": "PMID-8015553_T34", "type": "Entity", "text": [ "binding motifs" ], "offsets": [ [ 708, 722 ] ], "normalized": [] }, { "id": "PMID-8015553_T35", "type": "Entity", "text": [ "half-sites" ], "offsets": [ [ 743, 753 ] ], "normalized": [] }, { "id": "PMID-8015553_T36", "type": "Entity", "text": [ "3 kb 5'-flanking DNA" ], "offsets": [ [ 1341, 1361 ] ], "normalized": [] }, { "id": "PMID-8015553_T37", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1466, 1474 ] ], "normalized": [] }, { "id": "PMID-8015553_T38", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1530, 1538 ] ], "normalized": [] }, { "id": "PMID-8015553_T39", "type": "Entity", "text": [ "3 kb 5'-flanking region" ], "offsets": [ [ 1607, 1630 ] ], "normalized": [] }, { "id": "PMID-8015553_T40", "type": "Entity", "text": [ "dPRL promoter" ], "offsets": [ [ 1638, 1651 ] ], "normalized": [] }, { "id": "PMID-8015553_T41", "type": "Entity", "text": [ "elements" ], "offsets": [ [ 1668, 1676 ] ], "normalized": [] }, { "id": "PMID-8015553_T42", "type": "Entity", "text": [ "3 kb 5'-flanking DNA" ], "offsets": [ [ 1900, 1920 ] ], "normalized": [] }, { "id": "PMID-8015553_T43", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1977, 1985 ] ], "normalized": [] }, { "id": "PMID-8015553_T44", "type": "Entity", "text": [ "cAMP" ], "offsets": [ [ 2267, 2271 ] ], "normalized": [] }, { "id": "PMID-8015553_T45", "type": "Entity", "text": [ "cAMP" ], "offsets": [ [ 2353, 2357 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-8015553_1", "entity_ids": [ "PMID-8015553_T3", "PMID-8015553_T4" ] }, { "id": "PMID-8015553_2", "entity_ids": [ "PMID-8015553_T9", "PMID-8015553_T10" ] } ]

[ { "id": "PMID-8015553_R1", "type": "Protein-Component", "arg1_id": "PMID-8015553_T3", "arg2_id": "PMID-8015553_T31", "normalized": [] }, { "id": "PMID-8015553_R2", "type": "Protein-Component", "arg1_id": "PMID-8015553_T3", "arg2_id": "PMID-8015553_T30", "normalized": [] }, { "id": "PMID-8015553_R3", "type": "Protein-Component", "arg1_id": "PMID-8015553_T3", "arg2_id": "PMID-8015553_T29", "normalized": [] }, { "id": "PMID-8015553_R4", "type": "Protein-Component", "arg1_id": "PMID-8015553_T6", "arg2_id": "PMID-8015553_T32", "normalized": [] }, { "id": "PMID-8015553_R5", "type": "Protein-Component", "arg1_id": "PMID-8015553_T6", "arg2_id": "PMID-8015553_T33", "normalized": [] }, { "id": "PMID-8015553_R6", "type": "Protein-Component", "arg1_id": "PMID-8015553_T17", "arg2_id": "PMID-8015553_T36", "normalized": [] }, { "id": "PMID-8015553_R7", "type": "Protein-Component", "arg1_id": "PMID-8015553_T19", "arg2_id": "PMID-8015553_T37", "normalized": [] }, { "id": "PMID-8015553_R8", "type": "Protein-Component", "arg1_id": "PMID-8015553_T20", "arg2_id": "PMID-8015553_T38", "normalized": [] }, { "id": "PMID-8015553_R9", "type": "Protein-Component", "arg1_id": "PMID-8015553_T24", "arg2_id": "PMID-8015553_T42", "normalized": [] }, { "id": "PMID-8015553_R10", "type": "Protein-Component", "arg1_id": "PMID-8015553_T24", "arg2_id": "PMID-8015553_T43", "normalized": [] } ]

[ { "id": "PMID-8773576__text", "type": "abstract", "text": [ "The role of early growth response gene 1 (egr-1) in regulation of the immune response. \nThe induction of immediate early genes in cells of the immune system is critical to determining the ultimate outcome of exposure to antigen. The importance of many of these genes relates to the role their transcription factor products play in dictating patterns of expression of downstream, function-related genes. Evidence from several systems indicates that the immediate early gene, egr-1 may be of particular importance in the immune system. Recently, the egr-1 promoter has been shown to be highly responsive to the diverse biochemical signals generated by antigen and cytokines in cells of the immune system. Furthermore, an important role for egr-1 in determining the differentiation pathway of myeloid cell precursors has been recently elaborated. Finally, potential targets of regulation by the zinc-finger transcription factor encoded by egr-1 include the interleukin-2, CD44, ICAM-1, and tumor necrosis factor genes. The role of egr-1 in regulation of the immune response will be discussed in the context of these recent studies.\n" ], "offsets": [ [ 0, 1129 ] ] } ]

[ { "id": "PMID-8773576_T1", "type": "Protein", "text": [ "early growth response gene 1" ], "offsets": [ [ 12, 40 ] ], "normalized": [] }, { "id": "PMID-8773576_T2", "type": "Protein", "text": [ "egr-1" ], "offsets": [ [ 42, 47 ] ], "normalized": [] }, { "id": "PMID-8773576_T3", "type": "Protein", "text": [ "egr-1" ], "offsets": [ [ 474, 479 ] ], "normalized": [] }, { "id": "PMID-8773576_T4", "type": "Protein", "text": [ "egr-1" ], "offsets": [ [ 548, 553 ] ], "normalized": [] }, { "id": "PMID-8773576_T5", "type": "Protein", "text": [ "egr-1" ], "offsets": [ [ 738, 743 ] ], "normalized": [] }, { "id": "PMID-8773576_T6", "type": "Protein", "text": [ "egr-1" ], "offsets": [ [ 936, 941 ] ], "normalized": [] }, { "id": "PMID-8773576_T7", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 954, 967 ] ], "normalized": [] }, { "id": "PMID-8773576_T8", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 969, 973 ] ], "normalized": [] }, { "id": "PMID-8773576_T9", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 975, 981 ] ], "normalized": [] }, { "id": "PMID-8773576_T10", "type": "Protein", "text": [ "tumor necrosis factor" ], "offsets": [ [ 987, 1008 ] ], "normalized": [] }, { "id": "PMID-8773576_T11", "type": "Protein", "text": [ "egr-1" ], "offsets": [ [ 1028, 1033 ] ], "normalized": [] }, { "id": "PMID-8773576_T12", "type": "Entity", "text": [ "immediate early genes" ], "offsets": [ [ 105, 126 ] ], "normalized": [] }, { "id": "PMID-8773576_T13", "type": "Entity", "text": [ "function-related genes" ], "offsets": [ [ 379, 401 ] ], "normalized": [] }, { "id": "PMID-8773576_T14", "type": "Entity", "text": [ "immediate early gene" ], "offsets": [ [ 452, 472 ] ], "normalized": [] }, { "id": "PMID-8773576_T15", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 554, 562 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-8773576_1", "entity_ids": [ "PMID-8773576_T1", "PMID-8773576_T2" ] } ]

[ { "id": "PMID-8773576_R1", "type": "Protein-Component", "arg1_id": "PMID-8773576_T4", "arg2_id": "PMID-8773576_T15", "normalized": [] } ]

[ { "id": "PMID-1945879__text", "type": "abstract", "text": [ "One base pair change abolishes the T cell-restricted activity of a kB-like proto-enhancer element from the interleukin 2 promoter. \nThe inducible, T cell-specific enhancers of murine and human Interleukin 2 (Il-2) genes contain the kB-like sequence GGGATTTCACC as an essential cis-acting enhancer motif. When cloned in multiple copies this so-called TCEd (distal T cell element) acts as an inducible proto-enhancer element in E14 T lymphoma cells, but not in HeLa cells. In extracts of induced, Il-2 secreting El4 cells three individual protein factors bind to TCEd DNA. The binding of the most prominent factor, named TCF-1 (T cell factor 1), is correlated with the proto-enhancer activity of TCEd. TCF-1 consists of two polypeptides of about 50 kD and 105 kD; the former seems to be related to the 50 kD polypeptide of NF-kB. Purified NF-kB is also able to bind to the TCEd, but TCF-1 binds stronger than NF-kB to TCEd DNA. The conversion of the TCEd to a 'perfect' NF-kB binding site leads to a tighter binding of NF-kB to TCEd DNA and, as a functional consequence, to the activity of the 'converted' TCEd motifs in HeLa cells. Thus, the substitution of the underlined A residue to a C within the GGGATTTCACC motif abolishes its T cell-restricted activity and leads to its functioning in both El4 cells and HeLa cells. These results indicate that lymphocyte-specific factors binding to the TCEd are involved in the control of T cell specific-transcription of the Il-2 gene.\n" ], "offsets": [ [ 0, 1477 ] ] } ]

[ { "id": "PMID-1945879_T1", "type": "Protein", "text": [ "interleukin 2" ], "offsets": [ [ 107, 120 ] ], "normalized": [] }, { "id": "PMID-1945879_T2", "type": "Protein", "text": [ "Interleukin 2" ], "offsets": [ [ 193, 206 ] ], "normalized": [] }, { "id": "PMID-1945879_T3", "type": "Protein", "text": [ "Il-2" ], "offsets": [ [ 208, 212 ] ], "normalized": [] }, { "id": "PMID-1945879_T4", "type": "Protein", "text": [ "Il-2" ], "offsets": [ [ 495, 499 ] ], "normalized": [] }, { "id": "PMID-1945879_T5", "type": "Protein", "text": [ "TCF-1" ], "offsets": [ [ 619, 624 ] ], "normalized": [] }, { "id": "PMID-1945879_T6", "type": "Protein", "text": [ "T cell factor 1" ], "offsets": [ [ 626, 641 ] ], "normalized": [] }, { "id": "PMID-1945879_T7", "type": "Protein", "text": [ "TCF-1" ], "offsets": [ [ 700, 705 ] ], "normalized": [] }, { "id": "PMID-1945879_T8", "type": "Protein", "text": [ "TCF-1" ], "offsets": [ [ 881, 886 ] ], "normalized": [] }, { "id": "PMID-1945879_T9", "type": "Protein", "text": [ "Il-2" ], "offsets": [ [ 1466, 1470 ] ], "normalized": [] }, { "id": "PMID-1945879_T10", "type": "Entity", "text": [ "kB-like proto-enhancer element" ], "offsets": [ [ 67, 97 ] ], "normalized": [] }, { "id": "PMID-1945879_T11", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 121, 129 ] ], "normalized": [] }, { "id": "PMID-1945879_T12", "type": "Entity", "text": [ "T cell-specific enhancers" ], "offsets": [ [ 147, 172 ] ], "normalized": [] }, { "id": "PMID-1945879_T13", "type": "Entity", "text": [ "kB-like sequence" ], "offsets": [ [ 232, 248 ] ], "normalized": [] }, { "id": "PMID-1945879_T14", "type": "Entity", "text": [ "GGGATTTCACC" ], "offsets": [ [ 249, 260 ] ], "normalized": [] }, { "id": "PMID-1945879_T15", "type": "Entity", "text": [ "essential cis-acting enhancer motif" ], "offsets": [ [ 267, 302 ] ], "normalized": [] }, { "id": "PMID-1945879_T16", "type": "Entity", "text": [ "TCEd" ], "offsets": [ [ 350, 354 ] ], "normalized": [] }, { "id": "PMID-1945879_T17", "type": "Entity", "text": [ "distal T cell element" ], "offsets": [ [ 356, 377 ] ], "normalized": [] }, { "id": "PMID-1945879_T18", "type": "Entity", "text": [ "proto-enhancer element" ], "offsets": [ [ 400, 422 ] ], "normalized": [] }, { "id": "PMID-1945879_T19", "type": "Entity", "text": [ "TCEd DNA" ], "offsets": [ [ 561, 569 ] ], "normalized": [] }, { "id": "PMID-1945879_T20", "type": "Entity", "text": [ "TCEd" ], "offsets": [ [ 694, 698 ] ], "normalized": [] }, { "id": "PMID-1945879_T21", "type": "Entity", "text": [ "polypeptides" ], "offsets": [ [ 722, 734 ] ], "normalized": [] }, { "id": "PMID-1945879_T22", "type": "Entity", "text": [ "50 kD" ], "offsets": [ [ 744, 749 ] ], "normalized": [] }, { "id": "PMID-1945879_T23", "type": "Entity", "text": [ "105 kD" ], "offsets": [ [ 754, 760 ] ], "normalized": [] }, { "id": "PMID-1945879_T24", "type": "Entity", "text": [ "NF-kB" ], "offsets": [ [ 837, 842 ] ], "normalized": [] }, { "id": "PMID-1945879_T25", "type": "Entity", "text": [ "TCEd" ], "offsets": [ [ 871, 875 ] ], "normalized": [] }, { "id": "PMID-1945879_T26", "type": "Entity", "text": [ "NF-kB" ], "offsets": [ [ 907, 912 ] ], "normalized": [] }, { "id": "PMID-1945879_T27", "type": "Entity", "text": [ "TCEd DNA" ], "offsets": [ [ 916, 924 ] ], "normalized": [] }, { "id": "PMID-1945879_T28", "type": "Entity", "text": [ "TCEd" ], "offsets": [ [ 948, 952 ] ], "normalized": [] }, { "id": "PMID-1945879_T29", "type": "Entity", "text": [ "'perfect' NF-kB binding site" ], "offsets": [ [ 958, 986 ] ], "normalized": [] }, { "id": "PMID-1945879_T30", "type": "Entity", "text": [ "NF-kB" ], "offsets": [ [ 968, 973 ] ], "normalized": [] }, { "id": "PMID-1945879_T31", "type": "Entity", "text": [ "NF-kB" ], "offsets": [ [ 1017, 1022 ] ], "normalized": [] }, { "id": "PMID-1945879_T32", "type": "Entity", "text": [ "TCEd DNA" ], "offsets": [ [ 1026, 1034 ] ], "normalized": [] }, { "id": "PMID-1945879_T33", "type": "Entity", "text": [ "'converted' TCEd motifs" ], "offsets": [ [ 1092, 1115 ] ], "normalized": [] }, { "id": "PMID-1945879_T34", "type": "Entity", "text": [ "TCEd" ], "offsets": [ [ 1104, 1108 ] ], "normalized": [] }, { "id": "PMID-1945879_T35", "type": "Entity", "text": [ "A" ], "offsets": [ [ 1172, 1173 ] ], "normalized": [] }, { "id": "PMID-1945879_T36", "type": "Entity", "text": [ "C" ], "offsets": [ [ 1187, 1188 ] ], "normalized": [] }, { "id": "PMID-1945879_T37", "type": "Entity", "text": [ "GGGATTTCACC motif" ], "offsets": [ [ 1200, 1217 ] ], "normalized": [] }, { "id": "PMID-1945879_T38", "type": "Entity", "text": [ "TCEd" ], "offsets": [ [ 1393, 1397 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-1945879_1", "entity_ids": [ "PMID-1945879_T2", "PMID-1945879_T3" ] }, { "id": "PMID-1945879_2", "entity_ids": [ "PMID-1945879_T5", "PMID-1945879_T6" ] } ]

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[ { "id": "PMID-10438731__text", "type": "abstract", "text": [ "C/EBPbeta and GATA-1 synergistically regulate activity of the eosinophil granule major basic protein promoter: implication for C/EBPbeta activity in eosinophil gene expression. \nEosinophil granule major basic protein (MBP) is expressed exclusively in eosinophils and basophils in hematopoietic cells. In our previous study, we demonstrated a major positive regulatory role for GATA-1 and a negative regulatory role for GATA-2 in MBP gene transcription. Further analysis of the MBP promoter region identified a C/EBP (CCAAT/enhancer-binding protein) consensus binding site 6 bp upstream of the functional GATA-binding site in the MBP gene. In the cell line HT93A, which is capable of differentiating towards both the eosinophil and neutrophil lineages in response to retinoic acid (RA), C/EBPalpha mRNA expression decreased significantly concomitant with eosinophilic and neutrophilic differentiation, whereas C/EBPbeta expression was markedly increased. Electrophoretic mobility shift assays (EMSAs) showed that recombinant C/EBPbeta protein could bind to the potential C/EBP-binding site (bp -90 to -82) in the MBP promoter. Furthermore, we have demonstrated that both C/EBPbeta and GATA-1 can bind simultaneously to the C/EBP- and GATA-binding sites in the MBP promoter. To determine the functionality of both the C/EBP- and GATA- binding sites, we analyzed whether C/EBPbeta and GATA-1 can stimulate the MBP promoter in the C/EBPbeta and GATA-1 negative Jurkat T-cell line. Cotransfection with C/EBPbeta and GATA-1 expression vectors produced a 5-fold increase compared with cotransfection with the C/EBPbeta or GATA-1 expression vectors individually. In addition, GST pull-down experiments demonstrated a physical interaction between human GATA-1 and C/EBPbeta. Expression of FOG (riend ATA), which binds to GATA-1 and acts as a cofactor for GATA-binding proteins, decreased transactivation activity of GATA-1 for the MBP promoter in a dose-dependent manner. Our results provide the first evidence that both GATA-1 and C/EBPbeta synergistically transactivate the promoter of an eosinophil-specific granule protein gene and that FOG may act as a negative cofactor for the eosinophil lineage, unlike its positively regulatory function for the erythroid and megakaryocyte lineages.\n" ], "offsets": [ [ 0, 2283 ] ] } ]

[ { "id": "PMID-10438731_T1", "type": "Protein", "text": [ "C/EBPbeta" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "PMID-10438731_T2", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 14, 20 ] ], "normalized": [] }, { "id": "PMID-10438731_T3", "type": "Protein", "text": [ "eosinophil granule major basic protein" ], "offsets": [ [ 62, 100 ] ], "normalized": [] }, { "id": "PMID-10438731_T4", "type": "Protein", "text": [ "C/EBPbeta" ], "offsets": [ [ 127, 136 ] ], "normalized": [] }, { "id": "PMID-10438731_T5", "type": "Protein", "text": [ "Eosinophil granule major basic protein" ], "offsets": [ [ 178, 216 ] ], "normalized": [] }, { "id": "PMID-10438731_T6", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 218, 221 ] ], "normalized": [] }, { "id": "PMID-10438731_T7", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 377, 383 ] ], "normalized": [] }, { "id": "PMID-10438731_T8", "type": "Protein", "text": [ "GATA-2" ], "offsets": [ [ 419, 425 ] ], "normalized": [] }, { "id": "PMID-10438731_T9", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 429, 432 ] ], "normalized": [] }, { "id": "PMID-10438731_T10", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 477, 480 ] ], "normalized": [] }, { "id": "PMID-10438731_T11", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 629, 632 ] ], "normalized": [] }, { "id": "PMID-10438731_T12", "type": "Protein", "text": [ "C/EBPalpha" ], "offsets": [ [ 786, 796 ] ], "normalized": [] }, { "id": "PMID-10438731_T13", "type": "Protein", "text": [ "C/EBPbeta" ], "offsets": [ [ 909, 918 ] ], "normalized": [] }, { "id": "PMID-10438731_T14", "type": "Protein", "text": [ "C/EBPbeta" ], "offsets": [ [ 1024, 1033 ] ], "normalized": [] }, { "id": "PMID-10438731_T15", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 1112, 1115 ] ], "normalized": [] }, { "id": "PMID-10438731_T16", "type": "Protein", "text": [ "C/EBPbeta" ], "offsets": [ [ 1170, 1179 ] ], "normalized": [] }, { "id": "PMID-10438731_T17", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1184, 1190 ] ], "normalized": [] }, { "id": "PMID-10438731_T18", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 1259, 1262 ] ], "normalized": [] }, { "id": "PMID-10438731_T19", "type": "Protein", "text": [ "C/EBPbeta" ], "offsets": [ [ 1368, 1377 ] ], "normalized": [] }, { "id": "PMID-10438731_T20", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1382, 1388 ] ], "normalized": [] }, { "id": "PMID-10438731_T21", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 1407, 1410 ] ], "normalized": [] }, { "id": "PMID-10438731_T22", "type": "Protein", "text": [ "C/EBPbeta" ], "offsets": [ [ 1427, 1436 ] ], "normalized": [] }, { "id": "PMID-10438731_T23", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1441, 1447 ] ], "normalized": [] }, { "id": "PMID-10438731_T24", "type": "Protein", "text": [ "C/EBPbeta" ], "offsets": [ [ 1497, 1506 ] ], "normalized": [] }, { "id": "PMID-10438731_T25", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1511, 1517 ] ], "normalized": [] }, { "id": "PMID-10438731_T26", "type": "Protein", "text": [ "C/EBPbeta" ], "offsets": [ [ 1602, 1611 ] ], "normalized": [] }, { "id": "PMID-10438731_T27", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1615, 1621 ] ], "normalized": [] }, { "id": "PMID-10438731_T28", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1744, 1750 ] ], "normalized": [] }, { "id": "PMID-10438731_T29", "type": "Protein", "text": [ "C/EBPbeta" ], "offsets": [ [ 1755, 1764 ] ], "normalized": [] }, { "id": "PMID-10438731_T30", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1812, 1818 ] ], "normalized": [] }, { "id": "PMID-10438731_T31", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1907, 1913 ] ], "normalized": [] }, { "id": "PMID-10438731_T32", "type": "Protein", "text": [ "MBP" ], "offsets": [ [ 1922, 1925 ] ], "normalized": [] }, { "id": "PMID-10438731_T33", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 2012, 2018 ] ], "normalized": [] }, { "id": "PMID-10438731_T34", "type": "Protein", "text": [ "C/EBPbeta" ], "offsets": [ [ 2023, 2032 ] ], "normalized": [] }, { "id": "PMID-10438731_T35", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 101, 109 ] ], "normalized": [] }, { "id": "PMID-10438731_T36", "type": "Entity", "text": [ "eosinophil gene" ], "offsets": [ [ 149, 164 ] ], "normalized": [] }, { "id": "PMID-10438731_T37", "type": "Entity", "text": [ "promoter region" ], "offsets": [ [ 481, 496 ] ], "normalized": [] }, { "id": "PMID-10438731_T38", "type": "Entity", "text": [ "C/EBP (CCAAT/enhancer-binding protein) consensus binding site" ], "offsets": [ [ 510, 571 ] ], "normalized": [] }, { "id": "PMID-10438731_T39", "type": "Entity", "text": [ "GATA-binding site" ], "offsets": [ [ 604, 621 ] ], "normalized": [] }, { "id": "PMID-10438731_T40", "type": "Entity", "text": [ "C/EBP-binding site" ], "offsets": [ [ 1070, 1088 ] ], "normalized": [] }, { "id": "PMID-10438731_T41", "type": "Entity", "text": [ "bp -90 to -82" ], "offsets": [ [ 1090, 1103 ] ], "normalized": [] }, { "id": "PMID-10438731_T42", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1116, 1124 ] ], "normalized": [] }, { "id": "PMID-10438731_T43", "type": "Entity", "text": [ "binding sites" ], "offsets": [ [ 1238, 1251 ] ], "normalized": [] }, { "id": "PMID-10438731_T44", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1263, 1271 ] ], "normalized": [] }, { "id": "PMID-10438731_T45", "type": "Entity", "text": [ "binding sites" ], "offsets": [ [ 1333, 1346 ] ], "normalized": [] }, { "id": "PMID-10438731_T46", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1411, 1419 ] ], "normalized": [] }, { "id": "PMID-10438731_T47", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1926, 1934 ] ], "normalized": [] }, { "id": "PMID-10438731_T48", "type": "Entity", "text": [ "promoter of an eosinophil-specific granule protein gene" ], "offsets": [ [ 2067, 2122 ] ], "normalized": [] }, { "id": "PMID-10438731_T49", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 2067, 2075 ] ], "normalized": [] }, { "id": "PMID-10438731_T50", "type": "Entity", "text": [ "eosinophil-specific granule protein gene" ], "offsets": [ [ 2082, 2122 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-10438731_1", "entity_ids": [ "PMID-10438731_T5", "PMID-10438731_T6" ] } ]

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[ { "id": "PMID-9312192__text", "type": "abstract", "text": [ "Evidence that calcineurin is rate-limiting for primary human lymphocyte activation. \nCyclosporine (CsA) is both a clinical immunosuppressive drug and a probe to dissect intracellular signaling pathways. In vitro, CsA inhibits lymphocyte gene activation by inhibiting the phosphatase activity of calcineurin (CN). In clinical use, CsA treatment inhibits 50-75% of CN activity in circulating leukocytes. We modeled this degree of CN inhibition in primary human leukocytes in vitro in order to study the effect of partial CN inhibition on the downstream signaling events that lead to gene activation. In CsA-treated leukocytes stimulated by calcium ionophore, the degree of reduction in CN activity was accompanied by a similar degree of inhibition of each event tested: dephosphorylation of nuclear factor of activated T cell proteins, nuclear DNA binding, activation of a transfected reporter gene construct, IFN-gamma and IL-2 mRNA accumulation, and IFN-gamma production. Furthermore, the degree of CN inhibition was reflected by a similar degree of reduction in lymphocyte proliferation and IFN-gamma production in the allogeneic mixed lymphocyte cultures. These data support the conclusion that CN activity is rate-limiting for the activation of primary human T lymphocytes. Thus, the reduction of CN activity observed in CsA-treated patients is accompanied by a similar degree of reduction in lymphocyte gene activation, and accounts for the immunosuppression observed.\n" ], "offsets": [ [ 0, 1473 ] ] } ]

[ { "id": "PMID-9312192_T1", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 908, 917 ] ], "normalized": [] }, { "id": "PMID-9312192_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 922, 926 ] ], "normalized": [] }, { "id": "PMID-9312192_T3", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 950, 959 ] ], "normalized": [] }, { "id": "PMID-9312192_T4", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1092, 1101 ] ], "normalized": [] }, { "id": "PMID-9312192_T5", "type": "Entity", "text": [ "calcineurin" ], "offsets": [ [ 14, 25 ] ], "normalized": [] }, { "id": "PMID-9312192_T6", "type": "Entity", "text": [ "lymphocyte gene" ], "offsets": [ [ 226, 241 ] ], "normalized": [] }, { "id": "PMID-9312192_T7", "type": "Entity", "text": [ "calcineurin" ], "offsets": [ [ 295, 306 ] ], "normalized": [] }, { "id": "PMID-9312192_T8", "type": "Entity", "text": [ "CN" ], "offsets": [ [ 308, 310 ] ], "normalized": [] }, { "id": "PMID-9312192_T9", "type": "Entity", "text": [ "CN" ], "offsets": [ [ 363, 365 ] ], "normalized": [] }, { "id": "PMID-9312192_T10", "type": "Entity", "text": [ "CN" ], "offsets": [ [ 428, 430 ] ], "normalized": [] }, { "id": "PMID-9312192_T11", "type": "Entity", "text": [ "CN" ], "offsets": [ [ 519, 521 ] ], "normalized": [] }, { "id": "PMID-9312192_T12", "type": "Entity", "text": [ "CN" ], "offsets": [ [ 684, 686 ] ], "normalized": [] }, { "id": "PMID-9312192_T13", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 842, 845 ] ], "normalized": [] }, { "id": "PMID-9312192_T14", "type": "Entity", "text": [ "CN" ], "offsets": [ [ 999, 1001 ] ], "normalized": [] }, { "id": "PMID-9312192_T15", "type": "Entity", "text": [ "CN" ], "offsets": [ [ 1197, 1199 ] ], "normalized": [] }, { "id": "PMID-9312192_T16", "type": "Entity", "text": [ "CN" ], "offsets": [ [ 1300, 1302 ] ], "normalized": [] }, { "id": "PMID-9312192_T17", "type": "Entity", "text": [ "lymphocyte gene" ], "offsets": [ [ 1396, 1411 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-9649186__text", "type": "abstract", "text": [ "Oxidative stress suppresses transcription factor activities in stimulated lymphocytes. \nEffects of oxidative stress on stimulation-dependent signal transduction, leading to IL-2 expression, were studied. Purified quiescent human blood T lymphocytes were subjected to: (i) acute exposure to hydrogen peroxide; (ii) chronic exposure to hydrogen peroxide; and (iii) acute exposure to ionizing radiation. The cells were then stimulated for 6 h. DNA-binding activities (determined by the electrophoretic mobility shift assay) of three transcription factors: NFkappaB, AP-1 and NFAT, were abolished in the lymphocytes by all three modes of oxidative stress. The lymphocytes exhibited lipid peroxidation only upon exposure to the lowest level of hydrogen peroxide used (20 microM). All three modes of oxidative stress induced catalase activity in the lymphocytes. The only exception was hydrogen peroxide at 20 microM, which did not induce catalase activity. We conclude that: (i) suppression of specific transcription factor functions can potentially serve as a marker of exposure to oxidative stress and its effects on human lymphocytes; (ii) lipid peroxidation is only detectable in human lymphocytes upon exposure to weak oxidative stress which does not induce catalase activity; (iii) therefore, transcription factor DNA-binding activities are more sensitive to oxidative stress than lipid peroxidation.\n" ], "offsets": [ [ 0, 1402 ] ] } ]

[ { "id": "PMID-9649186_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 173, 177 ] ], "normalized": [] }, { "id": "PMID-9649186_T2", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 441, 444 ] ], "normalized": [] }, { "id": "PMID-9649186_T3", "type": "Entity", "text": [ "NFkappaB" ], "offsets": [ [ 553, 561 ] ], "normalized": [] }, { "id": "PMID-9649186_T4", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 563, 567 ] ], "normalized": [] }, { "id": "PMID-9649186_T5", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 1315, 1318 ] ], "normalized": [] } ]

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[ { "id": "PMID-9341756__text", "type": "abstract", "text": [ "Induction of endothelial cell surface adhesion molecules by tumor necrosis factor is blocked by protein tyrosine phosphatase inhibitors: role of the nuclear transcription factor NF-kappa B. \nRecent studies from our laboratory have indicated that protein tyrosine phosphatase (PTPase) inhibitors can down-modulate the tumor necrosis factor (TNF)-mediated activation of the nuclear transcription factor NF-kappa B in ML-1a, a monocytic cell line (Singh and Aggarwal, J. Biol. Chem. 1995: 270: 10631). Since TNF is one of the major inducers of various adhesion molecules in human endothelial cells and their expression is known to require the activation of NF-kappa B, we examined the effect of PTPase inhibitors on the TNF-mediated induction of intracellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and endothelial leukocyte adhesion molecule (ELAM)-1. Like ML-1a, human dermal microvessel endothelial cells (MVEC) treated with TNF rapidly activated (within 30 min) NF-kappa B; this effect was completely abolished by co-treatment with phenylarsine oxide (PAO), a specific inhibitor of PTPase. The induction of ICAM-1, VCAM-1, and ELAM-1 by TNF in MVEC occurred within 6 h and was also completely down-regulated by PAO in a dose-dependent manner. PAO was found to be effective even when added 3 h after TNF, suggesting a rapid mode of action of this inhibitor. Besides PAO, other inhibitors of PTPase, including pervanadate and diamide, also blocked TNF-dependent NF-kappa B activation and induction of all the three adhesion proteins. Consistent with these results, the attachment of monocytes to MVEC was also blocked by the PTPase inhibitors. Thus, overall, our results demonstrate that a PTPase is involved either directly or indirectly in the pathway leading to the induction of endothelial cell adhesion molecules by TNF. Because of their role in cell adhesion, PTPase may provide a novel target of drug development for treatment of inflammation, atherogenesis, and tumor metastasis.\n" ], "offsets": [ [ 0, 2017 ] ] } ]

[ { "id": "PMID-9341756_T1", "type": "Protein", "text": [ "intracellular adhesion molecule (ICAM)-1" ], "offsets": [ [ 743, 783 ] ], "normalized": [] }, { "id": "PMID-9341756_T2", "type": "Protein", "text": [ "vascular cell adhesion molecule (VCAM)-1" ], "offsets": [ [ 785, 825 ] ], "normalized": [] }, { "id": "PMID-9341756_T3", "type": "Protein", "text": [ "endothelial leukocyte adhesion molecule (ELAM)-1" ], "offsets": [ [ 830, 878 ] ], "normalized": [] }, { "id": "PMID-9341756_T4", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1138, 1144 ] ], "normalized": [] }, { "id": "PMID-9341756_T5", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1146, 1152 ] ], "normalized": [] }, { "id": "PMID-9341756_T6", "type": "Protein", "text": [ "ELAM-1" ], "offsets": [ [ 1158, 1164 ] ], "normalized": [] }, { "id": "PMID-9341756_T7", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 104, 112 ] ], "normalized": [] }, { "id": "PMID-9341756_T8", "type": "Entity", "text": [ "nuclear transcription factor" ], "offsets": [ [ 149, 177 ] ], "normalized": [] }, { "id": "PMID-9341756_T9", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 178, 188 ] ], "normalized": [] }, { "id": "PMID-9341756_T10", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 254, 262 ] ], "normalized": [] }, { "id": "PMID-9341756_T11", "type": "Entity", "text": [ "nuclear transcription factor" ], "offsets": [ [ 372, 400 ] ], "normalized": [] }, { "id": "PMID-9341756_T12", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 401, 411 ] ], "normalized": [] }, { "id": "PMID-9341756_T13", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 654, 664 ] ], "normalized": [] }, { "id": "PMID-9341756_T14", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 993, 1003 ] ], "normalized": [] }, { "id": "PMID-9341756_T15", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1491, 1501 ] ], "normalized": [] } ]

[]

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[]

[ { "id": "PMID-2023633__text", "type": "abstract", "text": [ "HIV enhancer activity perpetuated by NF-kappa B induction on infection of monocytes [see comments] \nPermissiveness to replication of human immunodeficiency virus (HIV) differs in T lymphocytes and macrophages. In T cells, HIV transcription is poorly detected in vivo. Cloned, normal T lymphocytes show very little, if any, basal activity of the HIV enhancer and low nuclear expression of NF-kappa B, a potent transcriptional activator of the HIV enhancer. In contrast, fixed tissue macrophages express detectable HIV proteins, indicating permanent virus transcription. One explanation for the perpetuation of virus infection in macrophages could be sustained nuclear NF-kappa B expression. However, the U937 monocytic cell line, which is fully permissive to HIV replication, is known to express only low levels of nuclear NF-kappa B. We show here that chronic HIV infection results in both induction of a nuclear factor with antigenic properties indistinguishable from those of NF-kappa B and permanently increased HIV enhancer activity. This phenomenon, which is independent of tumour necrosis factor, is associated with HIV replication, and is thus likely to explain at least in part the perpetuation of HIV infection in monocytes.\n" ], "offsets": [ [ 0, 1234 ] ] } ]

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[]

[]

[]

[ { "id": "PMID-10082134__text", "type": "abstract", "text": [ "Cobalt chloride-induced signaling in endothelium leading to the augmented adherence of sickle red blood cells and transendothelial migration of monocyte-like HL-60 cells is blocked by PAF-receptor antagonist. \nIn response to hypoxia, sickle red blood cells (SS RBC) and leukocytes exhibit increased adherence to the vascular endothelium, while diapedesis of leukocytes through the blood vessel increases. However, the cellular signaling pathway(s) caused by hypoxia is poorly understood. We utilized CoCl2 as a mimetic molecule for hypoxia to study cellular signaling pathways. We found that in human umbilical vein endothelial cells (HUVEC), CoCl2 at 2 mM concentration induced the surface expression of a subset of CAMs (VCAM-1) and activation of transcription factor NF-kappaB in the nuclear extracts of HUVEC. Furthermore, CoCl2 also caused time-dependent tyrosine phosphorylation of mitogen-activated protein (MAP) kinase isoform ERK2 without significantly affecting ERK1, indicating ERK2 is the preferred substrate for upstream kinase of the MAPK pathway. Inhibitors of MAP kinase (PD98059) or platelet-activating factor (PAF)- receptor antagonist (CV3988) inhibited the CoCl2-induced NF-kappaB activation and VCAM-1 expression. Augmented expression of VCAM-1 led to increased SS RBC adhesion, inhibitable by a VCAM-1 antibody. Additionally, CoCl2 caused a two- to threefold increase in the rate of transendothelial migration of monocyte-like HL-60 cells and a twentyfold increase in phosphorylation of platelet endothelial cell adhesion molecules (PECAM-1). The transendothelial migration of monocytes was inhibited by an antibody to PECAM-1. Both phosphorylation of PECAM-1 and transendothelial migration of monocytes in response to CoCl2 were inhibited by protein kinase inhibitor (GF109203X) and augmented by protein phosphatase inhibitor (Calyculin A). Our data suggests that CoCl2-induced cellular signals directing increased expression of VCAM-1 in HUVEC involve downstream activation of MAP kinase and NF-kappaB, while the phosphorylation of PECAM-1 occurs as a result of activation of PKC. We conclude that PAF-receptor antagonist inhibits the CoCl2- or hypoxia-induced increase in the adhesion of SS RBC, PECAM-1 phosphorylation, and the concomitant transendothelial migration of monocytes.\n" ], "offsets": [ [ 0, 2307 ] ] } ]

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[]

[]

[ { "id": "PMID-10082134_R1", "type": "Protein-Component", "arg1_id": "PMID-10082134_T3", "arg2_id": "PMID-10082134_T16", "normalized": [] } ]

[ { "id": "PMID-7565732__text", "type": "abstract", "text": [ "Transcriptional repression of the interleukin-2 gene by vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor. \nT-lymphocyte proliferation is suppressed by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D3, and is associated with a decrease in interleukin 2 (IL-2), gamma interferon, and granulocyte-macrophage colony-stimulating factor mRNA levels. We report here that 1,25(OH)2D3-mediated repression in Jurkat cells is cycloheximide resistant, suggesting that it is a direct transcriptional repressive effect on IL-2 expression by the vitamin D3 receptor (VDR). We therefore examined vitamin D3-mediated repression of activated IL-2 expression by cotransfecting Jurkat cells with IL-2 promoter/reporter constructs and a VDR overexpression vector and by DNA binding. We delineated an element conferring both DNA binding by the receptor in vitro and 1,25(OH)2D3-mediated repression in vivo to a short 40-bp region encompassing an important positive regulatory element, NF-AT-1, which is bound by a T-cell-specific transcription factor, NFATp, as well as by AP-1. VDR DNA-binding mutants were unable to either bind to this element in vitro or repress in vivo; the VDR DNA-binding domain alone, however, bound the element but also could not repress IL-2 expression. These results indicate that DNA binding by VDR is necessary but not sufficient to mediate IL-2 repression. By combining partially purified proteins in vitro, we observed the loss of the bound NFATp/AP-1-DNA complex upon inclusion of VDR or VDR-retinoid X receptor. Order of addition and off-rate experiments indicate that the VDR-retinoid X receptor heterodimer blocks NFATp/AP-1 complex formation and then stably associates with the NF-AT-1 element. This direct inhibition by a nuclear hormone receptor of transcriptional activators of the IL-2 gene may provide a mechanistic explanation of how vitamin derivatives can act as potent immunosuppressive agents.\n" ], "offsets": [ [ 0, 1988 ] ] } ]

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[]

[ { "id": "PMID-7565732_1", "entity_ids": [ "PMID-7565732_T3", "PMID-7565732_T4" ] }, { "id": "PMID-7565732_2", "entity_ids": [ "PMID-7565732_T6", "PMID-7565732_T7" ] } ]

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[ { "id": "PMID-8018558__text", "type": "abstract", "text": [ "Activation of early growth response 1 gene transcription and pp90rsk during induction of monocytic differentiation. \nThe present work has studied mechanisms responsible for induction of early growth response 1 (EGR-1) gene expression during monocytic differentiation of U-937 myeloid leukemia cells. Differentiation of U-937 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of the serine/threonine protein kinase C, was associated with transcriptional activation of EGR-1 promoter-reporter constructs. The EGR-1 promoter contains six CC(A/T)6GG (CArG) motifs. The two 5'-most distal CArG sequences conferred TPA inducibility. In contrast, there was little effect of TPA on EGR-1 transcription in a TPA-resistant U-937 cell variant, designated TUR. Treatment of both U-937 and TUR cells with okadaic acid, an inhibitor of serine/threonine protein phosphatases 1 and 2A, was associated with induction of monocytic differentiation and EGR-1 transcription through the 5'-most CArG element. Since these findings supported the involvement of serine/threonine protein phosphorylation in the regulation of EGR-1 expression, we studied activation of the 40S ribosomal protein S6 serine/threonine kinases, pp70S6K and pp90rsk. Although both kinases participate in regulating cell growth, there was no detectable activation of pp70S6K during TPA- or okadaic acid-induced monocytic differentiation. Moreover, rapamycin, an inhibitor of pp70S6K activation, had no effect on induction of EGR-1 expression. In contrast, analysis of pp90rsk activity by phosphorylation of a peptide derived from S6 protein demonstrated stimulation of this kinase in TPA-treated U-937, and not TUR, cells. Okadaic acid treatment of both cell types was associated with activation of pp90rsk.\n" ], "offsets": [ [ 0, 1776 ] ] } ]

[ { "id": "PMID-8018558_T1", "type": "Protein", "text": [ "early growth response 1" ], "offsets": [ [ 14, 37 ] ], "normalized": [] }, { "id": "PMID-8018558_T2", "type": "Protein", "text": [ "early growth response 1" ], "offsets": [ [ 186, 209 ] ], "normalized": [] }, { "id": "PMID-8018558_T3", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 211, 216 ] ], "normalized": [] }, { "id": "PMID-8018558_T4", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 485, 490 ] ], "normalized": [] }, { "id": "PMID-8018558_T5", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 525, 530 ] ], "normalized": [] }, { "id": "PMID-8018558_T6", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 692, 697 ] ], "normalized": [] }, { "id": "PMID-8018558_T7", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 951, 956 ] ], "normalized": [] }, { "id": "PMID-8018558_T8", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 1117, 1122 ] ], "normalized": [] }, { "id": "PMID-8018558_T9", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 1493, 1498 ] ], "normalized": [] }, { "id": "PMID-8018558_T10", "type": "Entity", "text": [ "serine" ], "offsets": [ [ 400, 406 ] ], "normalized": [] }, { "id": "PMID-8018558_T11", "type": "Entity", "text": [ "threonine" ], "offsets": [ [ 407, 416 ] ], "normalized": [] }, { "id": "PMID-8018558_T12", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 531, 539 ] ], "normalized": [] }, { "id": "PMID-8018558_T13", "type": "Entity", "text": [ "CC(A/T)6GG (CArG) motifs" ], "offsets": [ [ 553, 577 ] ], "normalized": [] }, { "id": "PMID-8018558_T14", "type": "Entity", "text": [ "5'-most distal CArG sequences" ], "offsets": [ [ 587, 616 ] ], "normalized": [] }, { "id": "PMID-8018558_T15", "type": "Entity", "text": [ "5'-most CArG element" ], "offsets": [ [ 983, 1003 ] ], "normalized": [] }, { "id": "PMID-8018558_T16", "type": "Entity", "text": [ "serine" ], "offsets": [ [ 1055, 1061 ] ], "normalized": [] }, { "id": "PMID-8018558_T17", "type": "Entity", "text": [ "threonine" ], "offsets": [ [ 1062, 1071 ] ], "normalized": [] }, { "id": "PMID-8018558_T18", "type": "Entity", "text": [ "serine" ], "offsets": [ [ 1189, 1195 ] ], "normalized": [] }, { "id": "PMID-8018558_T19", "type": "Entity", "text": [ "threonine" ], "offsets": [ [ 1196, 1205 ] ], "normalized": [] }, { "id": "PMID-8018558_T20", "type": "Entity", "text": [ "peptide derived from S6 protein" ], "offsets": [ [ 1577, 1608 ] ], "normalized": [] }, { "id": "PMID-8018558_T21", "type": "Entity", "text": [ "peptide" ], "offsets": [ [ 1577, 1584 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-8018558_1", "entity_ids": [ "PMID-8018558_T2", "PMID-8018558_T3" ] } ]

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[ { "id": "PMID-2234062__text", "type": "abstract", "text": [ "Cloning of a mitogen-inducible gene encoding a kappa B DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs. \nWe have cloned and characterized a mitogen-inducible gene isolated from human T cells that predicts a protein of 968 amino acids. The amino-terminal domain has regions homologous to the oncogene rel and to the developmentally important gene dorsal of Drosophila. The carboxy-terminal domain contains repeat structures found in a variety of proteins that are involved in cell-cycle control of yeast and in tissue differentiation in Drosophila and Ceanorhabditis elegans, as well as in the putative human oncogene bcl-3 and in the ankyrin protein. A truncated form of the product of this gene translated in vitro is a DNA-binding protein which interacts specifically with the kappa B binding site found in many inducible genes, including the enhancer in human immunodeficiency virus. This gene is yet another in a growing list of important regulatory molecules whose expression is transcriptionally induced upon cellular activation.\n" ], "offsets": [ [ 0, 1067 ] ] } ]

[ { "id": "PMID-2234062_T1", "type": "Entity", "text": [ "gene encoding a kappa B DNA-binding protein" ], "offsets": [ [ 31, 74 ] ], "normalized": [] }, { "id": "PMID-2234062_T2", "type": "Entity", "text": [ "rel oncogene" ], "offsets": [ [ 96, 108 ] ], "normalized": [] }, { "id": "PMID-2234062_T3", "type": "Entity", "text": [ "cell-cycle motifs" ], "offsets": [ [ 116, 133 ] ], "normalized": [] }, { "id": "PMID-2234062_T4", "type": "Entity", "text": [ "mitogen-inducible gene" ], "offsets": [ [ 171, 193 ] ], "normalized": [] }, { "id": "PMID-2234062_T5", "type": "Entity", "text": [ "gene" ], "offsets": [ [ 189, 193 ] ], "normalized": [] }, { "id": "PMID-2234062_T6", "type": "Entity", "text": [ "amino-terminal domain" ], "offsets": [ [ 270, 291 ] ], "normalized": [] }, { "id": "PMID-2234062_T7", "type": "Entity", "text": [ "oncogene rel" ], "offsets": [ [ 322, 334 ] ], "normalized": [] }, { "id": "PMID-2234062_T8", "type": "Entity", "text": [ "dorsal" ], "offsets": [ [ 377, 383 ] ], "normalized": [] }, { "id": "PMID-2234062_T9", "type": "Entity", "text": [ "carboxy-terminal domain" ], "offsets": [ [ 403, 426 ] ], "normalized": [] }, { "id": "PMID-2234062_T10", "type": "Entity", "text": [ "putative human oncogene bcl-3" ], "offsets": [ [ 624, 653 ] ], "normalized": [] }, { "id": "PMID-2234062_T11", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 752, 755 ] ], "normalized": [] }, { "id": "PMID-2234062_T12", "type": "Entity", "text": [ "kappa B binding site" ], "offsets": [ [ 810, 830 ] ], "normalized": [] }, { "id": "PMID-2234062_T13", "type": "Entity", "text": [ "inducible genes" ], "offsets": [ [ 845, 860 ] ], "normalized": [] }, { "id": "PMID-2234062_T14", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 876, 884 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-8934542__text", "type": "abstract", "text": [ "Cell specific expression of human Bruton's agammaglobulinemia tyrosine kinase gene (Btk) is regulated by Sp1- and Spi-1/PU.1-family members. \nBruton's agammaglobulinemia tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase involved in the human disease X-linked agammaglobulinemia (XLA). The gene is expressed in all hematopoietic cells with the exception of T-cells and plasma cells. For this expression pattern the first 280 bp upstream of the major transcriptional start site seems to be sufficient. In vitro footprinting analysis within this part of the promoter revealed two Sp1 binding sites as well as a PU-box. The transcription factor Spi-1/PU.1 as well as the closely related factor Spi-B bound to the PU-box in B-cells. In the erythroleukemia cell line K562, due to the absence of Spi-B, only PU.1 bound to the Btk promoter. Mutation of either site reduced the expression in transient transfection experiments. However, mutation of the PU box had no effect in the T-cell line Jurkat, where none of the Spi-1 family members is expressed. In addition Spi-B as well as PU.1 were able to transactivate Btk expression. In fetal liver of PU.1-/- mice, which lack lymphoid and myeloid cells, expression of Btk was reduced two- to threefold but not abolished. Collectively this study shows that expression of the Btk gene is regulated by the combined action of Sp1- and PU.1-family members.\n" ], "offsets": [ [ 0, 1396 ] ] } ]

[ { "id": "PMID-8934542_T1", "type": "Protein", "text": [ "Bruton's agammaglobulinemia tyrosine kinase" ], "offsets": [ [ 34, 77 ] ], "normalized": [] }, { "id": "PMID-8934542_T2", "type": "Protein", "text": [ "Btk" ], "offsets": [ [ 84, 87 ] ], "normalized": [] }, { "id": "PMID-8934542_T3", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 105, 108 ] ], "normalized": [] }, { "id": "PMID-8934542_T4", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 114, 119 ] ], "normalized": [] }, { "id": "PMID-8934542_T5", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 120, 124 ] ], "normalized": [] }, { "id": "PMID-8934542_T6", "type": "Protein", "text": [ "Bruton's agammaglobulinemia tyrosine kinase" ], "offsets": [ [ 142, 185 ] ], "normalized": [] }, { "id": "PMID-8934542_T7", "type": "Protein", "text": [ "Btk" ], "offsets": [ [ 187, 190 ] ], "normalized": [] }, { "id": "PMID-8934542_T8", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 582, 585 ] ], "normalized": [] }, { "id": "PMID-8934542_T9", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 646, 651 ] ], "normalized": [] }, { "id": "PMID-8934542_T10", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 652, 656 ] ], "normalized": [] }, { "id": "PMID-8934542_T11", "type": "Protein", "text": [ "Spi-B" ], "offsets": [ [ 695, 700 ] ], "normalized": [] }, { "id": "PMID-8934542_T12", "type": "Protein", "text": [ "Spi-B" ], "offsets": [ [ 794, 799 ] ], "normalized": [] }, { "id": "PMID-8934542_T13", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 806, 810 ] ], "normalized": [] }, { "id": "PMID-8934542_T14", "type": "Protein", "text": [ "Btk" ], "offsets": [ [ 824, 827 ] ], "normalized": [] }, { "id": "PMID-8934542_T15", "type": "Protein", "text": [ "Spi-1" ], "offsets": [ [ 1015, 1020 ] ], "normalized": [] }, { "id": "PMID-8934542_T16", "type": "Protein", "text": [ "Spi-B" ], "offsets": [ [ 1062, 1067 ] ], "normalized": [] }, { "id": "PMID-8934542_T17", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1079, 1083 ] ], "normalized": [] }, { "id": "PMID-8934542_T18", "type": "Protein", "text": [ "Btk" ], "offsets": [ [ 1111, 1114 ] ], "normalized": [] }, { "id": "PMID-8934542_T19", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1145, 1149 ] ], "normalized": [] }, { "id": "PMID-8934542_T20", "type": "Protein", "text": [ "Btk" ], "offsets": [ [ 1212, 1215 ] ], "normalized": [] }, { "id": "PMID-8934542_T21", "type": "Protein", "text": [ "Btk" ], "offsets": [ [ 1318, 1321 ] ], "normalized": [] }, { "id": "PMID-8934542_T22", "type": "Protein", "text": [ "Sp1" ], "offsets": [ [ 1366, 1369 ] ], "normalized": [] }, { "id": "PMID-8934542_T23", "type": "Protein", "text": [ "PU.1" ], "offsets": [ [ 1375, 1379 ] ], "normalized": [] }, { "id": "PMID-8934542_T24", "type": "Entity", "text": [ "280 bp upstream of the major transcriptional start site" ], "offsets": [ [ 425, 480 ] ], "normalized": [] }, { "id": "PMID-8934542_T25", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 560, 568 ] ], "normalized": [] }, { "id": "PMID-8934542_T26", "type": "Entity", "text": [ "binding sites" ], "offsets": [ [ 586, 599 ] ], "normalized": [] }, { "id": "PMID-8934542_T27", "type": "Entity", "text": [ "PU-box" ], "offsets": [ [ 613, 619 ] ], "normalized": [] }, { "id": "PMID-8934542_T28", "type": "Entity", "text": [ "PU-box" ], "offsets": [ [ 714, 720 ] ], "normalized": [] }, { "id": "PMID-8934542_T29", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 828, 836 ] ], "normalized": [] }, { "id": "PMID-8934542_T30", "type": "Entity", "text": [ "PU box" ], "offsets": [ [ 949, 955 ] ], "normalized": [] } ]

[]

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[ { "id": "PMID-10358756__text", "type": "abstract", "text": [ "Transcriptional regulation of T lymphocyte development and function. \nThe development and function of T lymphocytes are regulated tightly by signal transduction pathways that include specific cell-surface receptors, intracellular signaling molecules, and nuclear transcription factors. Since 1988, several families of functionally important T cell transcription factors have been identified. These include the Ikaros, LKLF, and GATA3 zinc-finger proteins; the Ets, CREB/ATF, and NF-kappa B/Rel/NFAT transcription factors; the Stat proteins; and HMG box transcription factors such as LEF1, TCF1, and Sox4. In this review, we summarize our current understanding of the transcriptional regulation of T cell development and function with particular emphasis on the results of recent gene targeting and transgenic experiments. In addition to increasing our understanding of the molecular pathways that regulate T cell development and function, these results have suggested novel targets for genetic and pharmacological manipulation of T cell immunity.\n" ], "offsets": [ [ 0, 1047 ] ] } ]

[ { "id": "PMID-10358756_T1", "type": "Protein", "text": [ "Ikaros" ], "offsets": [ [ 410, 416 ] ], "normalized": [] }, { "id": "PMID-10358756_T2", "type": "Protein", "text": [ "LKLF" ], "offsets": [ [ 418, 422 ] ], "normalized": [] }, { "id": "PMID-10358756_T3", "type": "Protein", "text": [ "GATA3" ], "offsets": [ [ 428, 433 ] ], "normalized": [] }, { "id": "PMID-10358756_T4", "type": "Protein", "text": [ "CREB" ], "offsets": [ [ 465, 469 ] ], "normalized": [] }, { "id": "PMID-10358756_T5", "type": "Protein", "text": [ "ATF" ], "offsets": [ [ 470, 473 ] ], "normalized": [] }, { "id": "PMID-10358756_T6", "type": "Protein", "text": [ "LEF1" ], "offsets": [ [ 583, 587 ] ], "normalized": [] }, { "id": "PMID-10358756_T7", "type": "Protein", "text": [ "TCF1" ], "offsets": [ [ 589, 593 ] ], "normalized": [] }, { "id": "PMID-10358756_T8", "type": "Protein", "text": [ "Sox4" ], "offsets": [ [ 599, 603 ] ], "normalized": [] }, { "id": "PMID-10358756_T9", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 479, 489 ] ], "normalized": [] }, { "id": "PMID-10358756_T10", "type": "Entity", "text": [ "Rel" ], "offsets": [ [ 490, 493 ] ], "normalized": [] }, { "id": "PMID-10358756_T11", "type": "Entity", "text": [ "NFAT transcription factors" ], "offsets": [ [ 494, 520 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-10358756_1", "entity_ids": [ "PMID-10358756_T4", "PMID-10358756_T5" ] } ]

[]

[ { "id": "PMID-1386962__text", "type": "abstract", "text": [ "The development of functionally responsive T cells. \nThe work reviewed in this article separates T cell development into four phases. First is an expansion phase prior to TCR rearrangement, which appears to be correlated with programming of at least some response genes for inducibility. This phase can occur to some extent outside of the thymus. However, the profound T cell deficit of nude mice indicates that the thymus is by far the most potent site for inducing the expansion per se, even if other sites can induce some response acquisition. Second is a controlled phase of TCR gene rearrangement. The details of the regulatory mechanism that selects particular loci for rearrangement are still not known. It seems that the rearrangement of the TCR gamma loci in the gamma delta lineage may not always take place at a developmental stage strictly equivalent to the rearrangement of TCR beta in the alpha beta lineage, and it is not clear just how early the two lineages diverge. In the TCR alpha beta lineage, however, the final gene rearrangement events are accompanied by rapid proliferation and an interruption in cellular response gene inducibility. The loss of conventional responsiveness is probably caused by alterations at the level of signaling, and may be a manifestation of the physiological state that is a precondition for selection. Third is the complex process of selection. Whereas peripheral T cells can undergo forms of positive selection (by antigen-driven clonal expansion) and negative selection (by abortive stimulation leading to anergy or death), neither is exactly the same phenomenon that occurs in the thymic cortex. Negative selection in the cortex appears to be a suicidal inversion of antigen responsiveness: instead of turning on IL-2 expression, the activated cell destroys its own chromatin. The genes that need to be induced for this response are not yet identified, but it is unquestionably a form of activation. It is interesting that in humans and rats, cortical thymocytes undergoing negative selection can still induce IL-2R alpha expression and even be rescued in vitro, if exogenous IL-2 is provided. Perhaps murine thymocytes are denied this form of rescue because they shut off IL-2R beta chain expression at an earlier stage or because they may be uncommonly Bcl-2 deficient (cf. Sentman et al., 1991; Strasser et al., 1991). Even so, medullary thymocytes remain at least partially susceptible to negative selection even as they continue to mature .\n" ], "offsets": [ [ 0, 2499 ] ] } ]

[ { "id": "PMID-1386962_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1766, 1770 ] ], "normalized": [] }, { "id": "PMID-1386962_T2", "type": "Protein", "text": [ "IL-2R alpha" ], "offsets": [ [ 2063, 2074 ] ], "normalized": [] }, { "id": "PMID-1386962_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 2129, 2133 ] ], "normalized": [] }, { "id": "PMID-1386962_T4", "type": "Protein", "text": [ "IL-2R beta chain" ], "offsets": [ [ 2226, 2242 ] ], "normalized": [] }, { "id": "PMID-1386962_T5", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 2308, 2313 ] ], "normalized": [] }, { "id": "PMID-1386962_T6", "type": "Entity", "text": [ "TCR" ], "offsets": [ [ 171, 174 ] ], "normalized": [] }, { "id": "PMID-1386962_T7", "type": "Entity", "text": [ "response genes" ], "offsets": [ [ 255, 269 ] ], "normalized": [] }, { "id": "PMID-1386962_T8", "type": "Entity", "text": [ "TCR gene" ], "offsets": [ [ 579, 587 ] ], "normalized": [] }, { "id": "PMID-1386962_T9", "type": "Entity", "text": [ "loci" ], "offsets": [ [ 667, 671 ] ], "normalized": [] }, { "id": "PMID-1386962_T10", "type": "Entity", "text": [ "TCR gamma loci" ], "offsets": [ [ 750, 764 ] ], "normalized": [] }, { "id": "PMID-1386962_T11", "type": "Entity", "text": [ "TCR beta" ], "offsets": [ [ 887, 895 ] ], "normalized": [] }, { "id": "PMID-1386962_T12", "type": "Entity", "text": [ "cellular response gene" ], "offsets": [ [ 1122, 1144 ] ], "normalized": [] }, { "id": "PMID-1386962_T13", "type": "Entity", "text": [ "chromatin" ], "offsets": [ [ 1819, 1828 ] ], "normalized": [] }, { "id": "PMID-1386962_T14", "type": "Entity", "text": [ "genes" ], "offsets": [ [ 1834, 1839 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-8054477__text", "type": "abstract", "text": [ "Positive and negative regulation of IL-2 gene expression: role of multiple regulatory sites. \nInterleukin 2 (IL-2) is an important lymphokine required in the process of T cell activation, proliferation, clonal expansion and differentiation. The IL-2 gene displays both T cell specific and inducible expression: it is only expressed in CD4+ T cells after antigenic or mitogenic stimulation. Several cis-acting regulatory sites are required for induction of the IL-2 gene after stimulation. In this study, we have analysed the function of these cis-acting regulatory sites in the context of the native IL-2 enhancer and promoter sequence. The results of this study suggest that the NFAT (-276 to -261), the distal octamer (-256 to -248) and the proximal octamer (-75 to -66) sites not only act as enhancers of IL-2 gene transcription in the presence of cellular stimulation, but also have a silencing effect on IL-2 gene expression in resting cells. Two other sites display disparate effects on IL-2 gene expression in different T leukemia cell lines: the distal purine box (-291 to -277) and the proximal purine box sites (-145 to -128). Finally, the AP-1 (-186 to -176) and the kappa B sites (-206 to -195) respond to different cellular activation in EL4 cells. The AP-1 site mediated the response to PMA stimulation while the kappa B site responded to IL-1 stimulation. These data suggest that the regulation of IL-2 gene expression is a complex process and multiple cis-acting regulatory sites interact to exert different effects in T cells representative of alternative stages of differentiation.\n" ], "offsets": [ [ 0, 1600 ] ] } ]

[ { "id": "PMID-8054477_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 36, 40 ] ], "normalized": [] }, { "id": "PMID-8054477_T2", "type": "Protein", "text": [ "Interleukin 2" ], "offsets": [ [ 94, 107 ] ], "normalized": [] }, { "id": "PMID-8054477_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 109, 113 ] ], "normalized": [] }, { "id": "PMID-8054477_T4", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 245, 249 ] ], "normalized": [] }, { "id": "PMID-8054477_T5", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 335, 338 ] ], "normalized": [] }, { "id": "PMID-8054477_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 460, 464 ] ], "normalized": [] }, { "id": "PMID-8054477_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 600, 604 ] ], "normalized": [] }, { "id": "PMID-8054477_T8", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 808, 812 ] ], "normalized": [] }, { "id": "PMID-8054477_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 909, 913 ] ], "normalized": [] }, { "id": "PMID-8054477_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 993, 997 ] ], "normalized": [] }, { "id": "PMID-8054477_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1413, 1417 ] ], "normalized": [] }, { "id": "PMID-8054477_T12", "type": "Entity", "text": [ "multiple regulatory sites" ], "offsets": [ [ 66, 91 ] ], "normalized": [] }, { "id": "PMID-8054477_T13", "type": "Entity", "text": [ "cis-acting regulatory sites" ], "offsets": [ [ 398, 425 ] ], "normalized": [] }, { "id": "PMID-8054477_T14", "type": "Entity", "text": [ "cis-acting regulatory sites" ], "offsets": [ [ 543, 570 ] ], "normalized": [] }, { "id": "PMID-8054477_T15", "type": "Entity", "text": [ "enhancer" ], "offsets": [ [ 605, 613 ] ], "normalized": [] }, { "id": "PMID-8054477_T16", "type": "Entity", "text": [ "promoter sequence" ], "offsets": [ [ 618, 635 ] ], "normalized": [] }, { "id": "PMID-8054477_T17", "type": "Entity", "text": [ "sites" ], "offsets": [ [ 773, 778 ] ], "normalized": [] }, { "id": "PMID-8054477_T18", "type": "Entity", "text": [ "distal purine box (-291 to -277)" ], "offsets": [ [ 1054, 1086 ] ], "normalized": [] }, { "id": "PMID-8054477_T19", "type": "Entity", "text": [ "proximal purine box sites (-145 to -128)" ], "offsets": [ [ 1095, 1135 ] ], "normalized": [] }, { "id": "PMID-8054477_T20", "type": "Entity", "text": [ "AP-1 (-186 to -176)" ], "offsets": [ [ 1150, 1169 ] ], "normalized": [] }, { "id": "PMID-8054477_T21", "type": "Entity", "text": [ "kappa B sites (-206 to -195)" ], "offsets": [ [ 1178, 1206 ] ], "normalized": [] }, { "id": "PMID-8054477_T22", "type": "Entity", "text": [ "AP-1 site" ], "offsets": [ [ 1266, 1275 ] ], "normalized": [] }, { "id": "PMID-8054477_T23", "type": "Entity", "text": [ "kappa B site" ], "offsets": [ [ 1327, 1339 ] ], "normalized": [] }, { "id": "PMID-8054477_T24", "type": "Entity", "text": [ "cis-acting regulatory sites" ], "offsets": [ [ 1468, 1495 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-8054477_1", "entity_ids": [ "PMID-8054477_T2", "PMID-8054477_T3" ] } ]

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[ { "id": "PMID-9834092__text", "type": "abstract", "text": [ "Regulation of NF-kappa B, AP-1, NFAT, and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF-kappa B p50. \nActivation of T lymphocytes by Ags or cytokines results in translocation of the transcription factors NF-kappa B, AP-1, NFAT, and STAT from the cytoplasm into the nucleus. The first step in the nuclear import process is recognition of a nuclear localization sequence (NLS) within the karyophilic protein by a cytoplasmic receptor such as the importin (karyopherin)-alpha subunit. The NLSs of NF-kappa B, AP-1, and NFAT differ and the NLS of STAT1 has not yet been identified. Herein we demonstrate that the inducible nuclear import of NF-kappa B, AP-1, NFAT, and STAT1 in Jurkat T lymphocytes is significantly inhibited by a cell-permeable peptide carrying the NLS of the NF-kappa B p50 subunit. NLS peptide-mediated disruption of the nuclear import of these transcription factors results in inhibition of I kappa B alpha and IL-2 gene expression, processes dependent on NF-kappa B or the combination of NF-kappa B, AP-1, and NFAT. Further, we show that inhibitory NLS peptide interacts in vitro with a cytoplasmic NLS receptor complex comprised of the Rch1/importin (karyopherin)-beta heterodimer expressed in Jurkat T cells. Taken together, these data indicate that the inducible nuclear import of NF-kappa B, AP-1, NFAT, and STAT1 in Jurkat T cells can be regulated by NLS peptide delivered noninvasively to the cytoplasm of Jurkat T cells to target members of the importin (karyopherin)-alpha beta NLS receptor complex.\n" ], "offsets": [ [ 0, 1602 ] ] } ]

[ { "id": "PMID-9834092_T1", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 42, 47 ] ], "normalized": [] }, { "id": "PMID-9834092_T2", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 172, 175 ] ], "normalized": [] }, { "id": "PMID-9834092_T3", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 741, 746 ] ], "normalized": [] }, { "id": "PMID-9834092_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 861, 864 ] ], "normalized": [] }, { "id": "PMID-9834092_T5", "type": "Protein", "text": [ "I kappa B alpha" ], "offsets": [ [ 984, 999 ] ], "normalized": [] }, { "id": "PMID-9834092_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1004, 1008 ] ], "normalized": [] }, { "id": "PMID-9834092_T7", "type": "Protein", "text": [ "Rch1" ], "offsets": [ [ 1231, 1235 ] ], "normalized": [] }, { "id": "PMID-9834092_T8", "type": "Protein", "text": [ "STAT1" ], "offsets": [ [ 1406, 1411 ] ], "normalized": [] }, { "id": "PMID-9834092_T9", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 14, 24 ] ], "normalized": [] }, { "id": "PMID-9834092_T10", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 26, 30 ] ], "normalized": [] }, { "id": "PMID-9834092_T11", "type": "Entity", "text": [ "peptide carrying the nuclear localization sequence of NF-kappa B p50" ], "offsets": [ [ 107, 175 ] ], "normalized": [] }, { "id": "PMID-9834092_T12", "type": "Entity", "text": [ "nuclear localization sequence" ], "offsets": [ [ 128, 157 ] ], "normalized": [] }, { "id": "PMID-9834092_T13", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 161, 171 ] ], "normalized": [] }, { "id": "PMID-9834092_T14", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 280, 290 ] ], "normalized": [] }, { "id": "PMID-9834092_T15", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 292, 296 ] ], "normalized": [] }, { "id": "PMID-9834092_T16", "type": "Entity", "text": [ "nuclear localization sequence" ], "offsets": [ [ 415, 444 ] ], "normalized": [] }, { "id": "PMID-9834092_T17", "type": "Entity", "text": [ "NLS" ], "offsets": [ [ 446, 449 ] ], "normalized": [] }, { "id": "PMID-9834092_T18", "type": "Entity", "text": [ "NLSs" ], "offsets": [ [ 562, 566 ] ], "normalized": [] }, { "id": "PMID-9834092_T19", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 570, 580 ] ], "normalized": [] }, { "id": "PMID-9834092_T20", "type": "Entity", "text": [ "NLS" ], "offsets": [ [ 612, 615 ] ], "normalized": [] }, { "id": "PMID-9834092_T21", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 713, 723 ] ], "normalized": [] }, { "id": "PMID-9834092_T22", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 725, 729 ] ], "normalized": [] }, { "id": "PMID-9834092_T23", "type": "Entity", "text": [ "cell-permeable peptide carrying the NLS of the NF-kappa B p50 subunit" ], "offsets": [ [ 803, 872 ] ], "normalized": [] }, { "id": "PMID-9834092_T24", "type": "Entity", "text": [ "cell-permeable peptide" ], "offsets": [ [ 803, 825 ] ], "normalized": [] }, { "id": "PMID-9834092_T25", "type": "Entity", "text": [ "NLS" ], "offsets": [ [ 839, 842 ] ], "normalized": [] }, { "id": "PMID-9834092_T26", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 850, 860 ] ], "normalized": [] }, { "id": "PMID-9834092_T27", "type": "Entity", "text": [ "NLS peptide" ], "offsets": [ [ 874, 885 ] ], "normalized": [] }, { "id": "PMID-9834092_T28", "type": "Entity", "text": [ "NLS" ], "offsets": [ [ 874, 877 ] ], "normalized": [] }, { "id": "PMID-9834092_T29", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1049, 1059 ] ], "normalized": [] }, { "id": "PMID-9834092_T30", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1082, 1092 ] ], "normalized": [] }, { "id": "PMID-9834092_T31", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 1094, 1098 ] ], "normalized": [] }, { "id": "PMID-9834092_T32", "type": "Entity", "text": [ "inhibitory NLS peptide" ], "offsets": [ [ 1132, 1154 ] ], "normalized": [] }, { "id": "PMID-9834092_T33", "type": "Entity", "text": [ "NLS" ], "offsets": [ [ 1143, 1146 ] ], "normalized": [] }, { "id": "PMID-9834092_T34", "type": "Entity", "text": [ "cytoplasmic NLS receptor complex" ], "offsets": [ [ 1181, 1213 ] ], "normalized": [] }, { "id": "PMID-9834092_T35", "type": "Entity", "text": [ "NLS" ], "offsets": [ [ 1193, 1196 ] ], "normalized": [] }, { "id": "PMID-9834092_T36", "type": "Entity", "text": [ "/importin (karyopherin)-beta heterodimer" ], "offsets": [ [ 1235, 1275 ] ], "normalized": [] }, { "id": "PMID-9834092_T37", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1378, 1388 ] ], "normalized": [] }, { "id": "PMID-9834092_T38", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 1390, 1394 ] ], "normalized": [] }, { "id": "PMID-9834092_T39", "type": "Entity", "text": [ "NLS peptide" ], "offsets": [ [ 1450, 1461 ] ], "normalized": [] }, { "id": "PMID-9834092_T40", "type": "Entity", "text": [ "NLS" ], "offsets": [ [ 1450, 1453 ] ], "normalized": [] }, { "id": "PMID-9834092_T41", "type": "Entity", "text": [ "NLS receptor complex" ], "offsets": [ [ 1580, 1600 ] ], "normalized": [] }, { "id": "PMID-9834092_T42", "type": "Entity", "text": [ "NLS" ], "offsets": [ [ 1580, 1583 ] ], "normalized": [] } ]

[]

[]

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[ { "id": "PMID-8018594__text", "type": "abstract", "text": [ "Effects of prostaglandin E2 on Th0-type human T cell clones: modulation of functions of nuclear proteins involved in cytokine production. \nThe effects of prostaglandin E2 (PGE2) on cytokine production and proliferation of the CD4+ human helper T cell clone SP-B21 were investigated. In cells stimulated with anti-CD3 mAb, PGE2 inhibited cell proliferation and the production of all the cytokines examined. Addition of rIL-2 fully restored the proliferative response and partially restored the production of IL-4 and IL-5, but not that of other cytokines. In contrast, in cells stimulated with phorbol myristate acetate (PMA)/A23187, PGE2 enhanced the production of IL-4 and IL-5, and only partially inhibited the production of other cytokines. Therefore, the effects of PGE2 vary depending on the mode of T cell activation, and the IL-4 and IL-5 are regulated differently from other cytokines. In a mobility shift assay, only the NF-kappa B (p50/p50) homodimer was observed in a complex formed with the kappa B sequence in unstimulated SP-B21 cells. When cells were stimulated with anti-CD3 mAb or PMA/A23187, a complex formation of NF-kappa B (p50/p65) heterodimer with the kappa B sequence was induced. Interestingly, PGE2 or di-butyryl (Bt2)cAMP abolished the binding of NF-kappa B (p50/p65) heterodimer to the kappa B sequence in cells stimulated with anti-CD3 mAb but not with PMA/A23187. Our results suggest that the target of PGE2 action is a component in the signal transduction pathway leading to the activation of protein kinase C. However, the inhibition of the T cell activation signals by PGE2 is selective. PGE2 enhanced the complex formation with NF-AT, AP-1 and CLE0 sequences when the cells were activated by either anti-CD3 mAb or PMA/A23187 stimulation. It seems therefore that PGE2, by elevating cAMP levels, interferes with the activation pathway for NF-kappa B but not for NF-AT, AP-1 or CLE0 binding protein.\n" ], "offsets": [ [ 0, 1932 ] ] } ]

[ { "id": "PMID-8018594_T1", "type": "Protein", "text": [ "CD4" ], "offsets": [ [ 226, 229 ] ], "normalized": [] }, { "id": "PMID-8018594_T2", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 507, 511 ] ], "normalized": [] }, { "id": "PMID-8018594_T3", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 516, 520 ] ], "normalized": [] }, { "id": "PMID-8018594_T4", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 665, 669 ] ], "normalized": [] }, { "id": "PMID-8018594_T5", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 674, 678 ] ], "normalized": [] }, { "id": "PMID-8018594_T6", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 832, 836 ] ], "normalized": [] }, { "id": "PMID-8018594_T7", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 841, 845 ] ], "normalized": [] }, { "id": "PMID-8018594_T8", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 942, 945 ] ], "normalized": [] }, { "id": "PMID-8018594_T9", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 946, 949 ] ], "normalized": [] }, { "id": "PMID-8018594_T10", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1145, 1148 ] ], "normalized": [] }, { "id": "PMID-8018594_T11", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1149, 1152 ] ], "normalized": [] }, { "id": "PMID-8018594_T12", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1286, 1289 ] ], "normalized": [] }, { "id": "PMID-8018594_T13", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1290, 1293 ] ], "normalized": [] }, { "id": "PMID-8018594_T14", "type": "Entity", "text": [ "homodimer" ], "offsets": [ [ 951, 960 ] ], "normalized": [] }, { "id": "PMID-8018594_T15", "type": "Entity", "text": [ "kappa B sequence" ], "offsets": [ [ 1003, 1019 ] ], "normalized": [] }, { "id": "PMID-8018594_T16", "type": "Entity", "text": [ "heterodimer" ], "offsets": [ [ 1154, 1165 ] ], "normalized": [] }, { "id": "PMID-8018594_T17", "type": "Entity", "text": [ "kappa B sequence" ], "offsets": [ [ 1175, 1191 ] ], "normalized": [] }, { "id": "PMID-8018594_T18", "type": "Entity", "text": [ "di-butyryl (Bt2)cAMP" ], "offsets": [ [ 1228, 1248 ] ], "normalized": [] }, { "id": "PMID-8018594_T19", "type": "Entity", "text": [ "cAMP" ], "offsets": [ [ 1244, 1248 ] ], "normalized": [] }, { "id": "PMID-8018594_T20", "type": "Entity", "text": [ "heterodimer" ], "offsets": [ [ 1295, 1306 ] ], "normalized": [] }, { "id": "PMID-8018594_T21", "type": "Entity", "text": [ "kappa B sequence" ], "offsets": [ [ 1314, 1330 ] ], "normalized": [] }, { "id": "PMID-8018594_T22", "type": "Entity", "text": [ "sequences" ], "offsets": [ [ 1683, 1692 ] ], "normalized": [] }, { "id": "PMID-8018594_T23", "type": "Entity", "text": [ "cAMP" ], "offsets": [ [ 1816, 1820 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-8018594_1", "entity_ids": [ "PMID-8018594_T8", "PMID-8018594_T9" ] } ]

[ { "id": "PMID-8018594_R1", "type": "Subunit-Complex", "arg1_id": "PMID-8018594_T8", "arg2_id": "PMID-8018594_T14", "normalized": [] }, { "id": "PMID-8018594_R2", "type": "Subunit-Complex", "arg1_id": "PMID-8018594_T10", "arg2_id": "PMID-8018594_T16", "normalized": [] }, { "id": "PMID-8018594_R3", "type": "Subunit-Complex", "arg1_id": "PMID-8018594_T11", "arg2_id": "PMID-8018594_T16", "normalized": [] }, { "id": "PMID-8018594_R4", "type": "Subunit-Complex", "arg1_id": "PMID-8018594_T12", "arg2_id": "PMID-8018594_T20", "normalized": [] }, { "id": "PMID-8018594_R5", "type": "Subunit-Complex", "arg1_id": "PMID-8018594_T13", "arg2_id": "PMID-8018594_T20", "normalized": [] } ]

[ { "id": "PMID-9933632__text", "type": "abstract", "text": [ "NF-kappaB activation is a critical regulator of human granulocyte apoptosis in vitro. \nDuring beneficial inflammation, potentially tissue-damaging granulocytes undergo apoptosis before being cleared by phagocytes in a non-phlogistic manner. Here we show that the rate of constitutive apoptosis in human neutrophils and eosinophils is greatly accelerated in both a rapid and concentration-dependent manner by the fungal metabolite gliotoxin, but not by its inactive analog methylthiogliotoxin. This induction of apoptosis was abolished by the caspase inhibitor zVAD-fmk, correlated with the inhibition of nuclear factor-kappa B (NF-kappaB), and was mimicked by a cell permeable inhibitory peptide of NF-kappaB, SN-50; other NF-kappaB inhibitors, curcumin and pyrrolidine dithiocarbamate; and the proteasome inhibitor, MG-132. Gliotoxin also augmented dramatically the early (2-6 h) pro-apoptotic effects of tumor necrosis factor-alpha (TNF-alpha) in neutrophils and unmasked the ability of TNF-alpha to induce eosinophil apoptosis. In neutrophils, TNF-alpha caused a gliotoxin-inhibitable activation of an inducible form of NF-kappaB, a response that may underlie the ability of TNF-alpha to delay apoptosis at later times (12-24 h) and limit its early killing effect. Furthermore, cycloheximide displayed a similar capacity to enhance TNF-alpha induced neutrophil apoptosis even at time points when cycloheximide alone had no pro-apoptotic effect, suggesting that NF-kappaB may regulate the production of protein(s) which protect neutrophils from the cytotoxic effects of TNF-alpha. These data shed light on the biochemical and molecular mechanisms regulating human granulocyte apoptosis and, in particular, indicate that the transcription factor NF-kappaB plays a crucial role in regulating the physiological cell death pathway in granulocytes.\n" ], "offsets": [ [ 0, 1846 ] ] } ]

[ { "id": "PMID-9933632_T1", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 906, 933 ] ], "normalized": [] }, { "id": "PMID-9933632_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 935, 944 ] ], "normalized": [] }, { "id": "PMID-9933632_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 989, 998 ] ], "normalized": [] }, { "id": "PMID-9933632_T4", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1047, 1056 ] ], "normalized": [] }, { "id": "PMID-9933632_T5", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1178, 1187 ] ], "normalized": [] }, { "id": "PMID-9933632_T6", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1335, 1344 ] ], "normalized": [] }, { "id": "PMID-9933632_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1572, 1581 ] ], "normalized": [] }, { "id": "PMID-9933632_T8", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 0, 9 ] ], "normalized": [] }, { "id": "PMID-9933632_T9", "type": "Entity", "text": [ "nuclear factor-kappa B" ], "offsets": [ [ 604, 626 ] ], "normalized": [] }, { "id": "PMID-9933632_T10", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 628, 637 ] ], "normalized": [] }, { "id": "PMID-9933632_T11", "type": "Entity", "text": [ "cell permeable inhibitory peptide" ], "offsets": [ [ 662, 695 ] ], "normalized": [] }, { "id": "PMID-9933632_T12", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 699, 708 ] ], "normalized": [] }, { "id": "PMID-9933632_T13", "type": "Entity", "text": [ "SN-50" ], "offsets": [ [ 710, 715 ] ], "normalized": [] }, { "id": "PMID-9933632_T14", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 723, 732 ] ], "normalized": [] }, { "id": "PMID-9933632_T15", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1123, 1132 ] ], "normalized": [] }, { "id": "PMID-9933632_T16", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1464, 1473 ] ], "normalized": [] }, { "id": "PMID-9933632_T17", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1747, 1756 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-9933632_1", "entity_ids": [ "PMID-9933632_T1", "PMID-9933632_T2" ] } ]

[]

[ { "id": "PMID-9057086__text", "type": "abstract", "text": [ "Differentiation of U-937 promonocytic cells by etoposide and ICRF-193, two antitumour DNA topoisomerase II inhibitors with different mechanisms of action. \nWe have compared the action on U-937 human promonocytic leukemia cells of two DNA topoisomerase II inhibitors, namely the epipodophyllotoxin etoposide and the bisdioxopiperazine ICRF-193. One hour pulse-treatment with 3 microM etoposide caused topoisomerase associated, primary DNA breakage, which was rapidly followed by apoptosis. By contrast, these effects were not observed upon pulse-treatment with 6 microM ICRF-193. However, continuous treatments with subcytotoxic concentrations of etoposide (0.15 microM) and ICRF-193 (0.3 microM) produced several similar effects, namely decreased cell proliferation, accumulation of cells at G2, increase in cell mass, and induction of differentiation. Under these conditions, etoposide produced a biphasic activation of protein kinase C, which consisted in an early transient activation (from hours 1 to 6) of the membrane-bound enzyme followed by a later activation (hour 48) of the total, membrane-bound and cytosolic enzyme. By contrast, ICRF-193 only provoked a late activation (from hours 72 to 96) of the total enzyme. When used at differentiation-inducing concentrations, both topoisomerase inhibitors caused a great stimulation of AP-1 binding activity, with maximum value at hour 12 in etoposide-treated cells and at hour 48 in ICRF-193-treated cells. By contrast, the binding activity of the NF-kappa(B) and EGR-1 transcription factors was little affected. It is concluded that topoisomerase II inhibitors may induce the differentiation of promonocytic cells, independently of their capacity to cause DNA strand breaks. However, there are other effects, such as the early activation of protein kinase C, which are probably derived from the production of primary DNA breakage by some anti-topoisomerase drugs.\n" ], "offsets": [ [ 0, 1920 ] ] } ]

[ { "id": "PMID-9057086_T1", "type": "Protein", "text": [ "EGR-1" ], "offsets": [ [ 1519, 1524 ] ], "normalized": [] }, { "id": "PMID-9057086_T2", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 1340, 1344 ] ], "normalized": [] }, { "id": "PMID-9057086_T3", "type": "Entity", "text": [ "NF-kappa(B)" ], "offsets": [ [ 1503, 1514 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-9763613__text", "type": "abstract", "text": [ "A critical role of the p75 tumor necrosis factor receptor (p75TNF-R) in organ inflammation independent of TNF, lymphotoxin alpha, or the p55TNF-R. \nDespite overwhelming evidence that enhanced production of the p75 tumor necrosis factor receptor (p75TNF-R) accompanies development of specific human inflammatory pathologies such as multi-organ failure during sepsis, inflammatory liver disease, pancreatitis, respiratory distress syndrome, or AIDS, the function of this receptor remains poorly defined in vivo. We show here that at levels relevant to human disease, production of the human p75TNF-R in transgenic mice results in a severe inflammatory syndrome involving mainly the pancreas, liver, kidney, and lung, and characterized by constitutively increased NF-kappaB activity in the peripheral blood mononuclear cell compartment. This process is shown to evolve independently of the presence of TNF, lymphotoxin alpha, or the p55TNF-R, although coexpression of a human TNF transgene accelerated pathology. These results establish an independent role for enhanced p75TNF-R production in the pathogenesis of inflammatory disease and implicate the direct involvement of this receptor in a wide range of human inflammatory pathologies.\n" ], "offsets": [ [ 0, 1236 ] ] } ]

[ { "id": "PMID-9763613_T1", "type": "Protein", "text": [ "p75 tumor necrosis factor receptor" ], "offsets": [ [ 23, 57 ] ], "normalized": [] }, { "id": "PMID-9763613_T2", "type": "Protein", "text": [ "p75TNF-R" ], "offsets": [ [ 59, 67 ] ], "normalized": [] }, { "id": "PMID-9763613_T3", "type": "Protein", "text": [ "lymphotoxin alpha" ], "offsets": [ [ 111, 128 ] ], "normalized": [] }, { "id": "PMID-9763613_T4", "type": "Protein", "text": [ "p55TNF-R" ], "offsets": [ [ 137, 145 ] ], "normalized": [] }, { "id": "PMID-9763613_T5", "type": "Protein", "text": [ "p75 tumor necrosis factor receptor" ], "offsets": [ [ 210, 244 ] ], "normalized": [] }, { "id": "PMID-9763613_T6", "type": "Protein", "text": [ "p75TNF-R" ], "offsets": [ [ 246, 254 ] ], "normalized": [] }, { "id": "PMID-9763613_T7", "type": "Protein", "text": [ "p75TNF-R" ], "offsets": [ [ 589, 597 ] ], "normalized": [] }, { "id": "PMID-9763613_T8", "type": "Protein", "text": [ "lymphotoxin alpha" ], "offsets": [ [ 904, 921 ] ], "normalized": [] }, { "id": "PMID-9763613_T9", "type": "Protein", "text": [ "p55TNF-R" ], "offsets": [ [ 930, 938 ] ], "normalized": [] }, { "id": "PMID-9763613_T10", "type": "Protein", "text": [ "p75TNF-R" ], "offsets": [ [ 1067, 1075 ] ], "normalized": [] }, { "id": "PMID-9763613_T11", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 761, 770 ] ], "normalized": [] }, { "id": "PMID-9763613_T12", "type": "Entity", "text": [ "human TNF transgene" ], "offsets": [ [ 967, 986 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-9763613_1", "entity_ids": [ "PMID-9763613_T1", "PMID-9763613_T2" ] }, { "id": "PMID-9763613_2", "entity_ids": [ "PMID-9763613_T5", "PMID-9763613_T6" ] } ]

[]

[ { "id": "PMID-8189531__text", "type": "abstract", "text": [ "Central nervous system-derived cells express a kappa B-binding activity that enhances human immunodeficiency virus type 1 transcription in vitro and facilitates TAR-independent transactivation by Tat. \nThe Tat protein of human immunodeficiency virus type 1 (HIV-1) is a potent activator of long terminal repeat-directed transcription. While in most cell types, activation requires interaction of Tat with the unusual transcription element TAR, astrocytic glial cells support TAR-independent transactivation of HIV-1 transcription by Tat. This alternative pathway of Tat activation is mediated by the viral enhancer, a kappa B domain capable of binding the prototypical form of the transcription factor nuclear factor kappa B (NF-kappa B) present in many cell types, including T lymphocytes. Tat transactivation mediated by the kappa B domain is sufficient to allow replication of TAR-deleted mutant HIV-1 in astrocytes. The present study demonstrates the existence of kappa B-specific binding factors present in human glial astrocytes that differ from prototypical NF-kappa B. The novel astrocyte-derived kappa B-binding activity is retained on an HIV-1 Tat affinity column, while prototypical NF-kappa B from Jurkat T cells is not. In vitro transcription studies demonstrate that astrocyte-derived kappa B-binding factors activate transcription of the HIV-1 long terminal repeat and that this activation is dependent on the kappa B domain. Moreover, TAR-independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with kappa B-binding activity. The importance of the central nervous system-enriched kappa B transcription factor in the regulation of HIV-1 expression is discussed.\n" ], "offsets": [ [ 0, 1752 ] ] } ]

[ { "id": "PMID-8189531_T1", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 196, 199 ] ], "normalized": [] }, { "id": "PMID-8189531_T2", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 206, 209 ] ], "normalized": [] }, { "id": "PMID-8189531_T3", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 396, 399 ] ], "normalized": [] }, { "id": "PMID-8189531_T4", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 533, 536 ] ], "normalized": [] }, { "id": "PMID-8189531_T5", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 566, 569 ] ], "normalized": [] }, { "id": "PMID-8189531_T6", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 791, 794 ] ], "normalized": [] }, { "id": "PMID-8189531_T7", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1154, 1157 ] ], "normalized": [] }, { "id": "PMID-8189531_T8", "type": "Entity", "text": [ "TAR" ], "offsets": [ [ 161, 164 ] ], "normalized": [] }, { "id": "PMID-8189531_T9", "type": "Entity", "text": [ "long terminal repeat" ], "offsets": [ [ 290, 310 ] ], "normalized": [] }, { "id": "PMID-8189531_T10", "type": "Entity", "text": [ "transcription element" ], "offsets": [ [ 417, 438 ] ], "normalized": [] }, { "id": "PMID-8189531_T11", "type": "Entity", "text": [ "TAR" ], "offsets": [ [ 439, 442 ] ], "normalized": [] }, { "id": "PMID-8189531_T12", "type": "Entity", "text": [ "TAR" ], "offsets": [ [ 475, 478 ] ], "normalized": [] }, { "id": "PMID-8189531_T13", "type": "Entity", "text": [ "viral enhancer" ], "offsets": [ [ 600, 614 ] ], "normalized": [] }, { "id": "PMID-8189531_T14", "type": "Entity", "text": [ "kappa B domain" ], "offsets": [ [ 618, 632 ] ], "normalized": [] }, { "id": "PMID-8189531_T15", "type": "Entity", "text": [ "transcription factor nuclear factor kappa B" ], "offsets": [ [ 681, 724 ] ], "normalized": [] }, { "id": "PMID-8189531_T16", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 726, 736 ] ], "normalized": [] }, { "id": "PMID-8189531_T17", "type": "Entity", "text": [ "kappa B domain" ], "offsets": [ [ 827, 841 ] ], "normalized": [] }, { "id": "PMID-8189531_T18", "type": "Entity", "text": [ "TAR" ], "offsets": [ [ 880, 883 ] ], "normalized": [] }, { "id": "PMID-8189531_T19", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1065, 1075 ] ], "normalized": [] }, { "id": "PMID-8189531_T20", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1194, 1204 ] ], "normalized": [] }, { "id": "PMID-8189531_T21", "type": "Entity", "text": [ "HIV-1 long terminal repeat" ], "offsets": [ [ 1353, 1379 ] ], "normalized": [] }, { "id": "PMID-8189531_T22", "type": "Entity", "text": [ "kappa B domain" ], "offsets": [ [ 1425, 1439 ] ], "normalized": [] }, { "id": "PMID-8189531_T23", "type": "Entity", "text": [ "TAR" ], "offsets": [ [ 1451, 1454 ] ], "normalized": [] }, { "id": "PMID-8189531_T24", "type": "Entity", "text": [ "HIV-1" ], "offsets": [ [ 1721, 1726 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-10080532__text", "type": "abstract", "text": [ "Inhibition of IL-4-inducible gene expression in human monocytes by type I and type II interferons. \nThe Th2-type cytokines, interleukin-4 (IL-4) and interleukin-13 (IL-13), induce expression of a distinct subset of genes in human monocytes, including FcepsilonRIIb (CD23), 15-lipoxygenase, IL-1 receptor antagonist (IL-1ra), and type I and type II IL-1 receptors (IL-1R). Type I interferons (IFN-alpha and IFN-beta) and type II interferon (IFN-gamma) inhibit induction of these genes by IL-4 and IL-13. However, the mechanism by which IFNs mediate this inhibition has not been defined. In this overview, we discuss the role of the transcription factor, STAT6 (signal transducer and activator of transcription-6) in mediating IL-4- and IL-13-induced gene expression in monocytes. We also discuss our recent findings that type I and type II IFNs suppress IL-4/IL-13-inducible gene expression by inhibiting tyrosine phosphorylation and nuclear translocation of STAT6. The ability of type I and type II IFNs to inhibit IL-4/IL-13-induced STAT6 activity is dose- and time-dependent, and is not unique to monocytes because IFNs induce the same effects in fibroblasts. Inhibition of STAT6 activity is not evident unless cells are preincubated with IFN for at least 1 h before IL-4 stimulation. Furthermore, inhibition can be blocked by actinomycin D, indicating a requirement for de novo transcription. We propose a model in which stimulation of monocytes by IFN activates de novo synthesis of an inhibitory factor, possibly one or more members of the SOCS/ SSI/CIS gene family, capable of suppressing activation of STAT6 by IL-4 and IL-13. Because STAT6 activation plays an essential role in IL-4/IL-13-induced gene expression, the ability of IFN-beta and IFN-gamma to inhibit STAT6 activity provides an explanation for how IFNs can suppress IL-4/IL-13-inducible gene expression.\n" ], "offsets": [ [ 0, 1874 ] ] } ]

[ { "id": "PMID-10080532_T1", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 14, 18 ] ], "normalized": [] }, { "id": "PMID-10080532_T2", "type": "Protein", "text": [ "interleukin-4" ], "offsets": [ [ 124, 137 ] ], "normalized": [] }, { "id": "PMID-10080532_T3", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 139, 143 ] ], "normalized": [] }, { "id": "PMID-10080532_T4", "type": "Protein", "text": [ "interleukin-13" ], "offsets": [ [ 149, 163 ] ], "normalized": [] }, { "id": "PMID-10080532_T5", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 165, 170 ] ], "normalized": [] }, { "id": "PMID-10080532_T6", "type": "Protein", "text": [ "FcepsilonRIIb" ], "offsets": [ [ 251, 264 ] ], "normalized": [] }, { "id": "PMID-10080532_T7", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 266, 270 ] ], "normalized": [] }, { "id": "PMID-10080532_T8", "type": "Protein", "text": [ "15-lipoxygenase" ], "offsets": [ [ 273, 288 ] ], "normalized": [] }, { "id": "PMID-10080532_T9", "type": "Protein", "text": [ "IL-1 receptor antagonist" ], "offsets": [ [ 290, 314 ] ], "normalized": [] }, { "id": "PMID-10080532_T10", "type": "Protein", "text": [ "IL-1ra" ], "offsets": [ [ 316, 322 ] ], "normalized": [] }, { "id": "PMID-10080532_T11", "type": "Protein", "text": [ "IFN-beta" ], "offsets": [ [ 406, 414 ] ], "normalized": [] }, { "id": "PMID-10080532_T12", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 440, 449 ] ], "normalized": [] }, { "id": "PMID-10080532_T13", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 487, 491 ] ], "normalized": [] }, { "id": "PMID-10080532_T14", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 496, 501 ] ], "normalized": [] }, { "id": "PMID-10080532_T15", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 653, 658 ] ], "normalized": [] }, { "id": "PMID-10080532_T16", "type": "Protein", "text": [ "signal transducer and activator of transcription-6" ], "offsets": [ [ 660, 710 ] ], "normalized": [] }, { "id": "PMID-10080532_T17", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 725, 729 ] ], "normalized": [] }, { "id": "PMID-10080532_T18", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 735, 740 ] ], "normalized": [] }, { "id": "PMID-10080532_T19", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 853, 857 ] ], "normalized": [] }, { "id": "PMID-10080532_T20", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 858, 863 ] ], "normalized": [] }, { "id": "PMID-10080532_T21", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 958, 963 ] ], "normalized": [] }, { "id": "PMID-10080532_T22", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1015, 1019 ] ], "normalized": [] }, { "id": "PMID-10080532_T23", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 1020, 1025 ] ], "normalized": [] }, { "id": "PMID-10080532_T24", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 1034, 1039 ] ], "normalized": [] }, { "id": "PMID-10080532_T25", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 1176, 1181 ] ], "normalized": [] }, { "id": "PMID-10080532_T26", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1269, 1273 ] ], "normalized": [] }, { "id": "PMID-10080532_T27", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 1609, 1614 ] ], "normalized": [] }, { "id": "PMID-10080532_T28", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1618, 1622 ] ], "normalized": [] }, { "id": "PMID-10080532_T29", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 1627, 1632 ] ], "normalized": [] }, { "id": "PMID-10080532_T30", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 1642, 1647 ] ], "normalized": [] }, { "id": "PMID-10080532_T31", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1686, 1690 ] ], "normalized": [] }, { "id": "PMID-10080532_T32", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 1691, 1696 ] ], "normalized": [] }, { "id": "PMID-10080532_T33", "type": "Protein", "text": [ "IFN-beta" ], "offsets": [ [ 1737, 1745 ] ], "normalized": [] }, { "id": "PMID-10080532_T34", "type": "Protein", "text": [ "IFN-gamma" ], "offsets": [ [ 1750, 1759 ] ], "normalized": [] }, { "id": "PMID-10080532_T35", "type": "Protein", "text": [ "STAT6" ], "offsets": [ [ 1771, 1776 ] ], "normalized": [] }, { "id": "PMID-10080532_T36", "type": "Protein", "text": [ "IL-4" ], "offsets": [ [ 1836, 1840 ] ], "normalized": [] }, { "id": "PMID-10080532_T37", "type": "Protein", "text": [ "IL-13" ], "offsets": [ [ 1841, 1846 ] ], "normalized": [] }, { "id": "PMID-10080532_T38", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 904, 912 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-10080532_1", "entity_ids": [ "PMID-10080532_T2", "PMID-10080532_T3" ] }, { "id": "PMID-10080532_2", "entity_ids": [ "PMID-10080532_T4", "PMID-10080532_T5" ] }, { "id": "PMID-10080532_3", "entity_ids": [ "PMID-10080532_T6", "PMID-10080532_T7" ] }, { "id": "PMID-10080532_4", "entity_ids": [ "PMID-10080532_T9", "PMID-10080532_T10" ] }, { "id": "PMID-10080532_5", "entity_ids": [ "PMID-10080532_T15", "PMID-10080532_T16" ] } ]

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[ { "id": "PMID-9374642__text", "type": "abstract", "text": [ "Hypoxia enhances induction of endothelial ICAM-1: role for metabolic acidosis and proteasomes. \nIntercellular adhesion molecule 1 (ICAM-1) is an important molecule in promotion of polymorphonuclear neutrophil transendothelial migration during inflammation. Coincident with many inflammatory diseases is tissue hypoxia. Thus we hypothesized that combinations of hypoxia and inflammatory stimuli may differentially regulate expression of endothelial ICAM-1. Human endothelial cells were exposed to hypoxia in the presence or absence of added lipopolysaccharide (LPS) and examined for expression of functional ICAM-1. Although hypoxia alone did not induce ICAM-1, the combination of LPS and hypoxia enhanced (3 +/- 0.4-fold over normoxia) ICAM-1 expression. Combinations of hypoxia and LPS significantly increased lymphocyte binding, and such increases were inhibited by addition of anti-ICAM-1 antibodies or antisense oligonucleotides. Hypoxic endothelia showed a > 10-fold increase in sensitivity to inhibitors of proteasome activation, and combinations of hypoxia and LPS enhanced proteasome-dependent cytoplasmic-to-nuclear localization of the nuclear transcription factor-kappa B p65 (Rel A) subunit. Such proteasome activation correlated with hypoxia-evoked decreases in both extracellular and intracellular pH. We conclude from these studies that endothelial hypoxia provides a novel, proteasome-dependent stimulus for ICAM-1 induction.\n" ], "offsets": [ [ 0, 1441 ] ] } ]

[ { "id": "PMID-9374642_T1", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 42, 48 ] ], "normalized": [] }, { "id": "PMID-9374642_T2", "type": "Protein", "text": [ "Intercellular adhesion molecule 1" ], "offsets": [ [ 96, 129 ] ], "normalized": [] }, { "id": "PMID-9374642_T3", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 131, 137 ] ], "normalized": [] }, { "id": "PMID-9374642_T4", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 448, 454 ] ], "normalized": [] }, { "id": "PMID-9374642_T5", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 607, 613 ] ], "normalized": [] }, { "id": "PMID-9374642_T6", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 653, 659 ] ], "normalized": [] }, { "id": "PMID-9374642_T7", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 736, 742 ] ], "normalized": [] }, { "id": "PMID-9374642_T8", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 885, 891 ] ], "normalized": [] }, { "id": "PMID-9374642_T9", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1182, 1185 ] ], "normalized": [] }, { "id": "PMID-9374642_T10", "type": "Protein", "text": [ "Rel A" ], "offsets": [ [ 1187, 1192 ] ], "normalized": [] }, { "id": "PMID-9374642_T11", "type": "Protein", "text": [ "ICAM-1" ], "offsets": [ [ 1423, 1429 ] ], "normalized": [] }, { "id": "PMID-9374642_T12", "type": "Entity", "text": [ "proteasomes" ], "offsets": [ [ 82, 93 ] ], "normalized": [] }, { "id": "PMID-9374642_T13", "type": "Entity", "text": [ "antisense oligonucleotides" ], "offsets": [ [ 906, 932 ] ], "normalized": [] }, { "id": "PMID-9374642_T14", "type": "Entity", "text": [ "inhibitors of proteasome activation" ], "offsets": [ [ 999, 1034 ] ], "normalized": [] }, { "id": "PMID-9374642_T15", "type": "Entity", "text": [ "proteasome" ], "offsets": [ [ 1013, 1023 ] ], "normalized": [] }, { "id": "PMID-9374642_T16", "type": "Entity", "text": [ "proteasome" ], "offsets": [ [ 1081, 1091 ] ], "normalized": [] }, { "id": "PMID-9374642_T17", "type": "Entity", "text": [ "nuclear transcription factor-kappa B" ], "offsets": [ [ 1145, 1181 ] ], "normalized": [] }, { "id": "PMID-9374642_T18", "type": "Entity", "text": [ "proteasome" ], "offsets": [ [ 1208, 1218 ] ], "normalized": [] }, { "id": "PMID-9374642_T19", "type": "Entity", "text": [ "proteasome" ], "offsets": [ [ 1389, 1399 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-9374642_1", "entity_ids": [ "PMID-9374642_T2", "PMID-9374642_T3" ] }, { "id": "PMID-9374642_2", "entity_ids": [ "PMID-9374642_T9", "PMID-9374642_T10" ] } ]

[ { "id": "PMID-9374642_R1", "type": "Subunit-Complex", "arg1_id": "PMID-9374642_T9", "arg2_id": "PMID-9374642_T17", "normalized": [] } ]

[ { "id": "PMID-8871623__text", "type": "abstract", "text": [ "Induction of activator protein (AP)-1 and nuclear factor-kappaB by CD28 stimulation involves both phosphatidylinositol 3-kinase and acidic sphingomyelinase signals. \nA major obstacle in understanding the signaling events that follow CD28 receptor ligation arises from the fact that CD28 acts as a costimulus to TCR engagement, making it difficult to assess the relative contribution of CD28 signals as distinct from those of the TCR. To overcome this problem, we have exploited the observation that activated human T cell blasts can be stimulated via the CD28 surface molecule in the absence of antigenic challenge; thus, we have been able to observe the response of normal T cells to CD28 activation in isolation. Using this system, we observed that CD28 stimulation by B7-transfected CHO cells induced a proliferative response in T cells that was not accompanied by measurable IL-2 production. However, subsequent analysis of transcription factor generation revealed that B7 stimulation induced both activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) complexes, but not NF-AT. In contrast, engagement of the TCR by class II MHC/superantigen, either with or without CD28 ligation, resulted in the induction of NF-AT, AP-1, and NF-kappaB as well as IL-2 production. Using selective inhibitors, we investigated the signaling pathways involved in the CD28-mediated induction of AP-1 and NF-kappaB. This revealed that NF-kappaB generation was sensitive to chloroquine, an inhibitor of acidic sphingomyelinase, but not to the phosphatidylinositol 3-kinase inhibitor, wortmannin. In contrast, AP-1 generation was inhibited by wortmannin and was also variably sensitive to chloroquine. These data suggest that in activated normal T cells, CD28-derived signals can stimulate proliferation at least in part via NF-kappaB and AP-1 generation, and that this response uses both acidic sphingomyelinase and phosphatidylinositol 3-kinase-linked pathways.\n" ], "offsets": [ [ 0, 1956 ] ] } ]

[ { "id": "PMID-8871623_T1", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 67, 71 ] ], "normalized": [] }, { "id": "PMID-8871623_T2", "type": "Protein", "text": [ "acidic sphingomyelinase" ], "offsets": [ [ 132, 155 ] ], "normalized": [] }, { "id": "PMID-8871623_T3", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 233, 237 ] ], "normalized": [] }, { "id": "PMID-8871623_T4", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 282, 286 ] ], "normalized": [] }, { "id": "PMID-8871623_T5", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 386, 390 ] ], "normalized": [] }, { "id": "PMID-8871623_T6", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 555, 559 ] ], "normalized": [] }, { "id": "PMID-8871623_T7", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 685, 689 ] ], "normalized": [] }, { "id": "PMID-8871623_T8", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 751, 755 ] ], "normalized": [] }, { "id": "PMID-8871623_T9", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 771, 773 ] ], "normalized": [] }, { "id": "PMID-8871623_T10", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 879, 883 ] ], "normalized": [] }, { "id": "PMID-8871623_T11", "type": "Protein", "text": [ "B7" ], "offsets": [ [ 974, 976 ] ], "normalized": [] }, { "id": "PMID-8871623_T12", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1181, 1185 ] ], "normalized": [] }, { "id": "PMID-8871623_T13", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1263, 1267 ] ], "normalized": [] }, { "id": "PMID-8871623_T14", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1363, 1367 ] ], "normalized": [] }, { "id": "PMID-8871623_T15", "type": "Protein", "text": [ "acidic sphingomyelinase" ], "offsets": [ [ 1496, 1519 ] ], "normalized": [] }, { "id": "PMID-8871623_T16", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 1747, 1751 ] ], "normalized": [] }, { "id": "PMID-8871623_T17", "type": "Protein", "text": [ "acidic sphingomyelinase" ], "offsets": [ [ 1881, 1904 ] ], "normalized": [] }, { "id": "PMID-8871623_T18", "type": "Entity", "text": [ "activator protein (AP)-1" ], "offsets": [ [ 13, 37 ] ], "normalized": [] }, { "id": "PMID-8871623_T19", "type": "Entity", "text": [ "nuclear factor-kappaB" ], "offsets": [ [ 42, 63 ] ], "normalized": [] }, { "id": "PMID-8871623_T20", "type": "Entity", "text": [ "activator protein-1 (AP-1)" ], "offsets": [ [ 1002, 1028 ] ], "normalized": [] }, { "id": "PMID-8871623_T21", "type": "Entity", "text": [ "nuclear factor-kappaB (NF-kappaB) complexes" ], "offsets": [ [ 1033, 1076 ] ], "normalized": [] }, { "id": "PMID-8871623_T22", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 1232, 1236 ] ], "normalized": [] }, { "id": "PMID-8871623_T23", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1242, 1251 ] ], "normalized": [] }, { "id": "PMID-8871623_T24", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 1390, 1394 ] ], "normalized": [] }, { "id": "PMID-8871623_T25", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1399, 1408 ] ], "normalized": [] }, { "id": "PMID-8871623_T26", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1429, 1438 ] ], "normalized": [] }, { "id": "PMID-8871623_T27", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 1602, 1606 ] ], "normalized": [] }, { "id": "PMID-8871623_T28", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1817, 1826 ] ], "normalized": [] }, { "id": "PMID-8871623_T29", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 1831, 1835 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-9889197__text", "type": "abstract", "text": [ "Intranuclear targeted delivery of functional NF-kappaB by 70 kDa heat shock protein. \nThe 70 kDa heat shock protein (Hsp70) is a highly conserved, ubiquitous protein involved in chaperoning proteins to various cellular organelles. Here we show that when added exogenously to cells, Hsp70 is readily imported into both cytoplasmic and nuclear compartments in a cell-type-specific fashion. We exploited this ability of Hsp70 to deliver NF-kappaB, a key transcriptional regulator of inflammatory responses. We demonstrate that a fusion protein composed of a C-terminal Hsp70 peptide and the p50 subunit of NF-kappaB was directed into the nucleus of cells, could bind DNA specifically, and activated Igkappa expression and TNFalpha production. We therefore propose that Hsp70 can be used as a vehicle for intracytoplasmic and intranuclear delivery of proteins or DNA to modulate gene expression and thereby control immune responses.\n" ], "offsets": [ [ 0, 929 ] ] } ]

[ { "id": "PMID-9889197_T1", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 588, 591 ] ], "normalized": [] }, { "id": "PMID-9889197_T2", "type": "Protein", "text": [ "Igkappa" ], "offsets": [ [ 696, 703 ] ], "normalized": [] }, { "id": "PMID-9889197_T3", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 719, 727 ] ], "normalized": [] }, { "id": "PMID-9889197_T4", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 45, 54 ] ], "normalized": [] }, { "id": "PMID-9889197_T5", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 434, 443 ] ], "normalized": [] }, { "id": "PMID-9889197_T6", "type": "Entity", "text": [ "C-terminal Hsp70 peptide" ], "offsets": [ [ 555, 579 ] ], "normalized": [] }, { "id": "PMID-9889197_T7", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 603, 612 ] ], "normalized": [] }, { "id": "PMID-9889197_T8", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 664, 667 ] ], "normalized": [] }, { "id": "PMID-9889197_T9", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 859, 862 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-9889197_R1", "type": "Subunit-Complex", "arg1_id": "PMID-9889197_T1", "arg2_id": "PMID-9889197_T7", "normalized": [] } ]

[ { "id": "PMID-10221643__text", "type": "abstract", "text": [ "Tcf-1-mediated transcription in T lymphocytes: differential role for glycogen synthase kinase-3 in fibroblasts and T cells. \nBeta-catenin is the vertebrate homolog of the Drosophila segment polarity gene Armadillo and plays roles in both cell-cell adhesion and transduction of the Wnt signaling cascade. Recently, members of the Lef/Tcf transcription factor family have been identified as protein partners of beta-catenin, explaining how beta-catenin alters gene expression. Here we report that in T cells, Tcf-1 also becomes transcriptionally active through interaction with beta-catenin, suggesting that the Wnt signal transduction pathway is operational in T lymphocytes as well. However, although Wnt signals are known to inhibit the activity of the negative regulatory protein kinase glycogen synthase kinase-3beta (GSK-3beta), resulting in increased levels of beta-catenin, we find no evidence for involvement of GSK-3beta in Tcf-mediated transcription in T cells. That is, a dominant negative GSK-3beta does not specifically activate Tcf transcription and stimuli (lithium or phytohemagglutinin) that inhibit GSK-3beta activity also do not activate Tcf reporter genes. Thus, inhibition of GSK-3beta is insufficient to activate Tcf-dependent transcription in T lymphocytes. In contrast, in C57MG fibroblast cells, lithium inactivates GSK-3beta and induces Tcf-controlled transcription. This is the first demonstration that lithium can alter gene expression of Tcf-responsive genes, and points to a difference in regulation of Wnt signaling between fibroblasts and lymphocytes.\n" ], "offsets": [ [ 0, 1583 ] ] } ]

[ { "id": "PMID-10221643_T1", "type": "Protein", "text": [ "Tcf-1" ], "offsets": [ [ 0, 5 ] ], "normalized": [] }, { "id": "PMID-10221643_T2", "type": "Protein", "text": [ "glycogen synthase kinase-3" ], "offsets": [ [ 69, 95 ] ], "normalized": [] }, { "id": "PMID-10221643_T3", "type": "Protein", "text": [ "Beta-catenin" ], "offsets": [ [ 125, 137 ] ], "normalized": [] }, { "id": "PMID-10221643_T4", "type": "Protein", "text": [ "beta-catenin" ], "offsets": [ [ 409, 421 ] ], "normalized": [] }, { "id": "PMID-10221643_T5", "type": "Protein", "text": [ "beta-catenin" ], "offsets": [ [ 438, 450 ] ], "normalized": [] }, { "id": "PMID-10221643_T6", "type": "Protein", "text": [ "Tcf-1" ], "offsets": [ [ 507, 512 ] ], "normalized": [] }, { "id": "PMID-10221643_T7", "type": "Protein", "text": [ "beta-catenin" ], "offsets": [ [ 576, 588 ] ], "normalized": [] }, { "id": "PMID-10221643_T8", "type": "Protein", "text": [ "glycogen synthase kinase-3beta" ], "offsets": [ [ 789, 819 ] ], "normalized": [] }, { "id": "PMID-10221643_T9", "type": "Protein", "text": [ "GSK-3beta" ], "offsets": [ [ 821, 830 ] ], "normalized": [] }, { "id": "PMID-10221643_T10", "type": "Protein", "text": [ "beta-catenin" ], "offsets": [ [ 866, 878 ] ], "normalized": [] }, { "id": "PMID-10221643_T11", "type": "Protein", "text": [ "GSK-3beta" ], "offsets": [ [ 919, 928 ] ], "normalized": [] }, { "id": "PMID-10221643_T12", "type": "Protein", "text": [ "GSK-3beta" ], "offsets": [ [ 1000, 1009 ] ], "normalized": [] }, { "id": "PMID-10221643_T13", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 1083, 1101 ] ], "normalized": [] }, { "id": "PMID-10221643_T14", "type": "Protein", "text": [ "GSK-3beta" ], "offsets": [ [ 1116, 1125 ] ], "normalized": [] }, { "id": "PMID-10221643_T15", "type": "Protein", "text": [ "GSK-3beta" ], "offsets": [ [ 1196, 1205 ] ], "normalized": [] }, { "id": "PMID-10221643_T16", "type": "Protein", "text": [ "GSK-3beta" ], "offsets": [ [ 1340, 1349 ] ], "normalized": [] }, { "id": "PMID-10221643_T17", "type": "Protein", "text": [ "Tcf" ], "offsets": [ [ 1362, 1365 ] ], "normalized": [] }, { "id": "PMID-10221643_T18", "type": "Entity", "text": [ "Drosophila segment polarity gene" ], "offsets": [ [ 171, 203 ] ], "normalized": [] }, { "id": "PMID-10221643_T19", "type": "Entity", "text": [ "Armadillo" ], "offsets": [ [ 204, 213 ] ], "normalized": [] }, { "id": "PMID-10221643_T20", "type": "Entity", "text": [ "Tcf reporter genes" ], "offsets": [ [ 1156, 1174 ] ], "normalized": [] }, { "id": "PMID-10221643_T21", "type": "Entity", "text": [ "Tcf-responsive genes" ], "offsets": [ [ 1466, 1486 ] ], "normalized": [] }, { "id": "PMID-10221643_T22", "type": "Entity", "text": [ "Wnt" ], "offsets": [ [ 1532, 1535 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-10221643_1", "entity_ids": [ "PMID-10221643_T8", "PMID-10221643_T9" ] } ]

[]

[ { "id": "PMID-8183915__text", "type": "abstract", "text": [ "Alternative splicing of RNA transcripts encoded by the murine p105 NF-kappa B gene generates I kappa B gamma isoforms with different inhibitory activities. \nThe gene encoding the 105-kDa protein (p105) precursor of the p50 subunit of transcription factor NF-kappa B also encodes a p70 I kappa B protein, I kappa B gamma, which is identical to the C-terminal 607 amino acids of p105. Here we show that alternative RNA splicing generates I kappa B gamma isoforms with properties different from those of p70. One 63-kDa isoform, termed I kappa B gamma-1, which lacks 59 amino acids C-terminal to ankyrin repeat 7, has a novel 35-amino acid C terminus encoded by an alternative reading frame of the p105 gene. A 55-kDa isoform, I kappa B gamma-2, lacks the 190 C-terminal amino acids of p70I kappa B gamma. In contrast to p70I kappa B gamma, which is a cytoplasmic protein, I kappa B gamma-1 is found in both the cytoplasm and nucleus, whereas I kappa B gamma-2 is predominantly nuclear. The I kappa B gamma isoforms also display differences in specificity and affinity for Rel/NF-kappa B proteins. While p70I kappa B gamma inhibits p50-, p65-, and c-Rel-mediated transactivation and/or DNA binding, both I kappa B gamma-1 and I kappa B gamma-2 are specific for p50 and have different affinities for this subunit. The absence in I kappa B gamma-1 and I kappa B gamma-2 of a protein kinase A site whose phosphorylation modulates p70I kappa B gamma inhibitory activity suggests that alternative RNA splicing may be used to generate I kappa B gamma isoforms that respond differently to intracellular signals.\n" ], "offsets": [ [ 0, 1602 ] ] } ]

[ { "id": "PMID-8183915_T1", "type": "Protein", "text": [ "p105 NF-kappa B" ], "offsets": [ [ 62, 77 ] ], "normalized": [] }, { "id": "PMID-8183915_T2", "type": "Protein", "text": [ "I kappa B gamma" ], "offsets": [ [ 93, 108 ] ], "normalized": [] }, { "id": "PMID-8183915_T3", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 196, 200 ] ], "normalized": [] }, { "id": "PMID-8183915_T4", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 219, 222 ] ], "normalized": [] }, { "id": "PMID-8183915_T5", "type": "Protein", "text": [ "p70 I kappa B" ], "offsets": [ [ 281, 294 ] ], "normalized": [] }, { "id": "PMID-8183915_T6", "type": "Protein", "text": [ "I kappa B gamma" ], "offsets": [ [ 304, 319 ] ], "normalized": [] }, { "id": "PMID-8183915_T7", "type": "Protein", "text": [ "I kappa B gamma" ], "offsets": [ [ 436, 451 ] ], "normalized": [] }, { "id": "PMID-8183915_T8", "type": "Protein", "text": [ "I kappa B gamma-1" ], "offsets": [ [ 533, 550 ] ], "normalized": [] }, { "id": "PMID-8183915_T9", "type": "Protein", "text": [ "p105" ], "offsets": [ [ 695, 699 ] ], "normalized": [] }, { "id": "PMID-8183915_T10", "type": "Protein", "text": [ "I kappa B gamma-2" ], "offsets": [ [ 724, 741 ] ], "normalized": [] }, { "id": "PMID-8183915_T11", "type": "Protein", "text": [ "p70I kappa B gamma" ], "offsets": [ [ 783, 801 ] ], "normalized": [] }, { "id": "PMID-8183915_T12", "type": "Protein", "text": [ "p70I kappa B gamma" ], "offsets": [ [ 818, 836 ] ], "normalized": [] }, { "id": "PMID-8183915_T13", "type": "Protein", "text": [ "I kappa B gamma-1" ], "offsets": [ [ 870, 887 ] ], "normalized": [] }, { "id": "PMID-8183915_T14", "type": "Protein", "text": [ "I kappa B gamma-2" ], "offsets": [ [ 940, 957 ] ], "normalized": [] }, { "id": "PMID-8183915_T15", "type": "Protein", "text": [ "I kappa B gamma" ], "offsets": [ [ 988, 1003 ] ], "normalized": [] }, { "id": "PMID-8183915_T16", "type": "Protein", "text": [ "p70I kappa B gamma" ], "offsets": [ [ 1101, 1119 ] ], "normalized": [] }, { "id": "PMID-8183915_T17", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1129, 1132 ] ], "normalized": [] }, { "id": "PMID-8183915_T18", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1135, 1138 ] ], "normalized": [] }, { "id": "PMID-8183915_T19", "type": "Protein", "text": [ "c-Rel" ], "offsets": [ [ 1145, 1150 ] ], "normalized": [] }, { "id": "PMID-8183915_T20", "type": "Protein", "text": [ "I kappa B gamma-1" ], "offsets": [ [ 1201, 1218 ] ], "normalized": [] }, { "id": "PMID-8183915_T21", "type": "Protein", "text": [ "I kappa B gamma-2" ], "offsets": [ [ 1223, 1240 ] ], "normalized": [] }, { "id": "PMID-8183915_T22", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 1258, 1261 ] ], "normalized": [] }, { "id": "PMID-8183915_T23", "type": "Protein", "text": [ "I kappa B gamma-1" ], "offsets": [ [ 1325, 1342 ] ], "normalized": [] }, { "id": "PMID-8183915_T24", "type": "Protein", "text": [ "I kappa B gamma-2" ], "offsets": [ [ 1347, 1364 ] ], "normalized": [] }, { "id": "PMID-8183915_T25", "type": "Protein", "text": [ "p70I kappa B gamma" ], "offsets": [ [ 1424, 1442 ] ], "normalized": [] }, { "id": "PMID-8183915_T26", "type": "Protein", "text": [ "I kappa B gamma" ], "offsets": [ [ 1526, 1541 ] ], "normalized": [] }, { "id": "PMID-8183915_T27", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 255, 265 ] ], "normalized": [] }, { "id": "PMID-8183915_T28", "type": "Entity", "text": [ "C-terminal 607 amino acids" ], "offsets": [ [ 347, 373 ] ], "normalized": [] }, { "id": "PMID-8183915_T29", "type": "Entity", "text": [ "59 amino acids" ], "offsets": [ [ 564, 578 ] ], "normalized": [] }, { "id": "PMID-8183915_T30", "type": "Entity", "text": [ "ankyrin repeat 7" ], "offsets": [ [ 593, 609 ] ], "normalized": [] }, { "id": "PMID-8183915_T31", "type": "Entity", "text": [ "35-amino acid C terminus" ], "offsets": [ [ 623, 647 ] ], "normalized": [] }, { "id": "PMID-8183915_T32", "type": "Entity", "text": [ "alternative reading frame" ], "offsets": [ [ 662, 687 ] ], "normalized": [] }, { "id": "PMID-8183915_T33", "type": "Entity", "text": [ "190 C-terminal amino acids" ], "offsets": [ [ 753, 779 ] ], "normalized": [] }, { "id": "PMID-8183915_T34", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 1074, 1084 ] ], "normalized": [] }, { "id": "PMID-8183915_T35", "type": "Entity", "text": [ "protein kinase A site" ], "offsets": [ [ 1370, 1391 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-8183915_R1", "type": "Subunit-Complex", "arg1_id": "PMID-8183915_T4", "arg2_id": "PMID-8183915_T27", "normalized": [] }, { "id": "PMID-8183915_R2", "type": "Protein-Component", "arg1_id": "PMID-8183915_T9", "arg2_id": "PMID-8183915_T32", "normalized": [] }, { "id": "PMID-8183915_R3", "type": "Protein-Component", "arg1_id": "PMID-8183915_T8", "arg2_id": "PMID-8183915_T31", "normalized": [] }, { "id": "PMID-8183915_R4", "type": "Protein-Component", "arg1_id": "PMID-8183915_T9", "arg2_id": "PMID-8183915_T31", "normalized": [] }, { "id": "PMID-8183915_R5", "type": "Protein-Component", "arg1_id": "PMID-8183915_T10", "arg2_id": "PMID-8183915_T33", "normalized": [] }, { "id": "PMID-8183915_R6", "type": "Protein-Component", "arg1_id": "PMID-8183915_T11", "arg2_id": "PMID-8183915_T33", "normalized": [] } ]

[ { "id": "PMID-9834272__text", "type": "abstract", "text": [ "Epithelial cell-initiated inflammation plays a crucial role in early tissue damage in amebic infection of human intestine. \nBACKGROUND & AIMS: Entamoeba histolytica infection of the intestine can induce severe gut inflammation. The aims of this study were to assess the role of the host inflammatory response in the tissue damage observed with amebiasis and the role of the intestinal epithelial cell in initiating that response. METHODS: E. histolytica infection was established in human intestinal xenografts in severe combined immunodeficient (SCID-HU-INT) mice. Human intestinal epithelial cell inflammatory responses to amebic infection were inhibited by the intraluminal administration of an antisense oligonucleotide to the human p65 subunit of nuclear factor kappaB, and the role of neutrophils in tissue damage observed with amebiasis was studied by depleting neutrophils from SCID-HU-INT mice. RESULTS: Administration of the antisense oligonucleotide blocked the production of human interleukin 1beta and interleukin 8 by intestinal epithelial cells and inhibited neutrophil influx into the E. histolytica-infected intestinal xenografts. Inhibition of the gut inflammatory response by the antisense oligonucleotide or the depletion of neutrophils from SCID-HU- INT mice blocked the increase in intestinal permeability observed with amebic infection. CONCLUSIONS: Intestinal epithelial cells initiate an inflammatory response with resulting neutrophil-mediated tissue damage in response to E. histolytica infection; this inflammatory cascade can be blocked by inhibiting the transcription of genes regulated by nuclear factor kappaB.\n" ], "offsets": [ [ 0, 1643 ] ] } ]

[ { "id": "PMID-9834272_T1", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 737, 740 ] ], "normalized": [] }, { "id": "PMID-9834272_T2", "type": "Protein", "text": [ "interleukin 1beta" ], "offsets": [ [ 993, 1010 ] ], "normalized": [] }, { "id": "PMID-9834272_T3", "type": "Protein", "text": [ "interleukin 8" ], "offsets": [ [ 1015, 1028 ] ], "normalized": [] }, { "id": "PMID-9834272_T4", "type": "Entity", "text": [ "antisense oligonucleotide to the human p65 subunit" ], "offsets": [ [ 698, 748 ] ], "normalized": [] }, { "id": "PMID-9834272_T5", "type": "Entity", "text": [ "nuclear factor kappaB" ], "offsets": [ [ 752, 773 ] ], "normalized": [] }, { "id": "PMID-9834272_T6", "type": "Entity", "text": [ "antisense oligonucleotide" ], "offsets": [ [ 935, 960 ] ], "normalized": [] }, { "id": "PMID-9834272_T7", "type": "Entity", "text": [ "antisense oligonucleotide" ], "offsets": [ [ 1199, 1224 ] ], "normalized": [] }, { "id": "PMID-9834272_T8", "type": "Entity", "text": [ "genes regulated by nuclear factor kappaB" ], "offsets": [ [ 1601, 1641 ] ], "normalized": [] }, { "id": "PMID-9834272_T9", "type": "Entity", "text": [ "genes" ], "offsets": [ [ 1601, 1606 ] ], "normalized": [] }, { "id": "PMID-9834272_T10", "type": "Entity", "text": [ "nuclear factor kappaB" ], "offsets": [ [ 1620, 1641 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-9834272_R1", "type": "Subunit-Complex", "arg1_id": "PMID-9834272_T1", "arg2_id": "PMID-9834272_T5", "normalized": [] } ]

[ { "id": "PMID-8709191__text", "type": "abstract", "text": [ "oriP is essential for EBNA gene promoter activity in Epstein-Barr virus-immortalized lymphoblastoid cell lines. \nDuring Epstein-Barr virus latent infection of B lymphocytes in vitro, six viral nuclear antigens (EBNAs) are expressed from one of two promoters, Cp or Wp, whose activities are mutually exclusive. Upon infection, Wp is initially active, followed by a switch to Cp for the duration of latency. In this study, the region upstream of Cp was analyzed for the presence of cis elements involved in regulating the activities of the EBNA gene promoters in established in vitro immortalized lymphoblastoid cell lines (LCLs). It was determined that oriP, the origin for episomal maintenance during latency, is essential for efficient transcription initiation from either Cp or Wp in LCLs, as well as in some Burkitt's lymphoma cell lines. Deletion of the EBNA2-dependent enhancer located upstream of Cp resulted in a ca. two- to fivefold reduction in Cp activity in the LCLs assayed. More extensive deletion of sequences upstream of Cp, including the EBNA2-dependent enhancer, resulted in nearly complete loss of Cp activity. This loss of activity was shown to correlate with deletion of two CCAAT boxes, a proximal CCAAT box located at bp -61 to -65 and a distal CCAAT box located at bp -253 to -257, upstream of Cp. Site-directed mutagenesis of these cis elements demonstrated that Cp activity is highly dependent on the presence of a properly positioned CCAAT box, with the dependence on the distal CCAAT box apparent only when the proximal CCAAT box was deleted or mutated. Deletion of the glucocorticoid response elements located at ca. bp -850 upstream of Cp did not result in a significant loss in activity. In general, deletions which diminished Cp activity resulted in induction of Wp activity, consistent with suppression of Wp activity by transcriptional interference from Cp. The identification of oriP and the EBNA2-dependent enhancer as the major positive cis elements involved in regulating Cp activity in LCL suggests that EBNA gene transcription is largely autoregulated by EBNA 1 and EBNA 2.\n" ], "offsets": [ [ 0, 2113 ] ] } ]

[ { "id": "PMID-8709191_T1", "type": "Protein", "text": [ "oriP" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-8709191_T2", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 259, 261 ] ], "normalized": [] }, { "id": "PMID-8709191_T3", "type": "Protein", "text": [ "Wp" ], "offsets": [ [ 265, 267 ] ], "normalized": [] }, { "id": "PMID-8709191_T4", "type": "Protein", "text": [ "Wp" ], "offsets": [ [ 326, 328 ] ], "normalized": [] }, { "id": "PMID-8709191_T5", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 374, 376 ] ], "normalized": [] }, { "id": "PMID-8709191_T6", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 444, 446 ] ], "normalized": [] }, { "id": "PMID-8709191_T7", "type": "Protein", "text": [ "oriP" ], "offsets": [ [ 652, 656 ] ], "normalized": [] }, { "id": "PMID-8709191_T8", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 774, 776 ] ], "normalized": [] }, { "id": "PMID-8709191_T9", "type": "Protein", "text": [ "Wp" ], "offsets": [ [ 780, 782 ] ], "normalized": [] }, { "id": "PMID-8709191_T10", "type": "Protein", "text": [ "EBNA2" ], "offsets": [ [ 858, 863 ] ], "normalized": [] }, { "id": "PMID-8709191_T11", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 903, 905 ] ], "normalized": [] }, { "id": "PMID-8709191_T12", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 954, 956 ] ], "normalized": [] }, { "id": "PMID-8709191_T13", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 1036, 1038 ] ], "normalized": [] }, { "id": "PMID-8709191_T14", "type": "Protein", "text": [ "EBNA2" ], "offsets": [ [ 1054, 1059 ] ], "normalized": [] }, { "id": "PMID-8709191_T15", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 1116, 1118 ] ], "normalized": [] }, { "id": "PMID-8709191_T16", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 1317, 1319 ] ], "normalized": [] }, { "id": "PMID-8709191_T17", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 1387, 1389 ] ], "normalized": [] }, { "id": "PMID-8709191_T18", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 1665, 1667 ] ], "normalized": [] }, { "id": "PMID-8709191_T19", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 1757, 1759 ] ], "normalized": [] }, { "id": "PMID-8709191_T20", "type": "Protein", "text": [ "Wp" ], "offsets": [ [ 1794, 1796 ] ], "normalized": [] }, { "id": "PMID-8709191_T21", "type": "Protein", "text": [ "Wp" ], "offsets": [ [ 1838, 1840 ] ], "normalized": [] }, { "id": "PMID-8709191_T22", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 1887, 1889 ] ], "normalized": [] }, { "id": "PMID-8709191_T23", "type": "Protein", "text": [ "oriP" ], "offsets": [ [ 1913, 1917 ] ], "normalized": [] }, { "id": "PMID-8709191_T24", "type": "Protein", "text": [ "EBNA2" ], "offsets": [ [ 1926, 1931 ] ], "normalized": [] }, { "id": "PMID-8709191_T25", "type": "Protein", "text": [ "Cp" ], "offsets": [ [ 2009, 2011 ] ], "normalized": [] }, { "id": "PMID-8709191_T26", "type": "Protein", "text": [ "EBNA 1" ], "offsets": [ [ 2094, 2100 ] ], "normalized": [] }, { "id": "PMID-8709191_T27", "type": "Protein", "text": [ "EBNA 2" ], "offsets": [ [ 2105, 2111 ] ], "normalized": [] }, { "id": "PMID-8709191_T28", "type": "Entity", "text": [ "EBNA gene" ], "offsets": [ [ 22, 31 ] ], "normalized": [] }, { "id": "PMID-8709191_T29", "type": "Entity", "text": [ "promoters" ], "offsets": [ [ 248, 257 ] ], "normalized": [] }, { "id": "PMID-8709191_T30", "type": "Entity", "text": [ "cis elements" ], "offsets": [ [ 480, 492 ] ], "normalized": [] }, { "id": "PMID-8709191_T31", "type": "Entity", "text": [ "EBNA gene promoters" ], "offsets": [ [ 538, 557 ] ], "normalized": [] }, { "id": "PMID-8709191_T32", "type": "Entity", "text": [ "-dependent enhancer" ], "offsets": [ [ 863, 882 ] ], "normalized": [] }, { "id": "PMID-8709191_T33", "type": "Entity", "text": [ "-dependent enhancer" ], "offsets": [ [ 1059, 1078 ] ], "normalized": [] }, { "id": "PMID-8709191_T34", "type": "Entity", "text": [ "CCAAT boxes" ], "offsets": [ [ 1195, 1206 ] ], "normalized": [] }, { "id": "PMID-8709191_T35", "type": "Entity", "text": [ "proximal CCAAT box" ], "offsets": [ [ 1210, 1228 ] ], "normalized": [] }, { "id": "PMID-8709191_T36", "type": "Entity", "text": [ "bp -61 to -65" ], "offsets": [ [ 1240, 1253 ] ], "normalized": [] }, { "id": "PMID-8709191_T37", "type": "Entity", "text": [ "CCAAT box" ], "offsets": [ [ 1267, 1276 ] ], "normalized": [] }, { "id": "PMID-8709191_T38", "type": "Entity", "text": [ "-253 to -257" ], "offsets": [ [ 1291, 1303 ] ], "normalized": [] }, { "id": "PMID-8709191_T39", "type": "Entity", "text": [ "cis elements" ], "offsets": [ [ 1356, 1368 ] ], "normalized": [] }, { "id": "PMID-8709191_T40", "type": "Entity", "text": [ "CCAAT box" ], "offsets": [ [ 1460, 1469 ] ], "normalized": [] }, { "id": "PMID-8709191_T41", "type": "Entity", "text": [ "distal CCAAT box" ], "offsets": [ [ 1498, 1514 ] ], "normalized": [] }, { "id": "PMID-8709191_T42", "type": "Entity", "text": [ "CCAAT box" ], "offsets": [ [ 1505, 1514 ] ], "normalized": [] }, { "id": "PMID-8709191_T43", "type": "Entity", "text": [ "proximal CCAAT box" ], "offsets": [ [ 1538, 1556 ] ], "normalized": [] }, { "id": "PMID-8709191_T44", "type": "Entity", "text": [ "CCAAT box" ], "offsets": [ [ 1547, 1556 ] ], "normalized": [] }, { "id": "PMID-8709191_T45", "type": "Entity", "text": [ "ca. bp -850" ], "offsets": [ [ 1641, 1652 ] ], "normalized": [] }, { "id": "PMID-8709191_T46", "type": "Entity", "text": [ "-dependent enhancer" ], "offsets": [ [ 1931, 1950 ] ], "normalized": [] }, { "id": "PMID-8709191_T47", "type": "Entity", "text": [ "cis elements" ], "offsets": [ [ 1973, 1985 ] ], "normalized": [] }, { "id": "PMID-8709191_T48", "type": "Entity", "text": [ "EBNA gene" ], "offsets": [ [ 2042, 2051 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-8709191_R1", "type": "Protein-Component", "arg1_id": "PMID-8709191_T6", "arg2_id": "PMID-8709191_T30", "normalized": [] }, { "id": "PMID-8709191_R2", "type": "Protein-Component", "arg1_id": "PMID-8709191_T11", "arg2_id": "PMID-8709191_T32", "normalized": [] }, { "id": "PMID-8709191_R3", "type": "Protein-Component", "arg1_id": "PMID-8709191_T13", "arg2_id": "PMID-8709191_T33", "normalized": [] }, { "id": "PMID-8709191_R4", "type": "Protein-Component", "arg1_id": "PMID-8709191_T16", "arg2_id": "PMID-8709191_T37", "normalized": [] }, { "id": "PMID-8709191_R5", "type": "Protein-Component", "arg1_id": "PMID-8709191_T16", "arg2_id": "PMID-8709191_T34", "normalized": [] }, { "id": "PMID-8709191_R6", "type": "Protein-Component", "arg1_id": "PMID-8709191_T16", "arg2_id": "PMID-8709191_T36", "normalized": [] }, { "id": "PMID-8709191_R7", "type": "Protein-Component", "arg1_id": "PMID-8709191_T16", "arg2_id": "PMID-8709191_T35", "normalized": [] }, { "id": "PMID-8709191_R8", "type": "Protein-Component", "arg1_id": "PMID-8709191_T16", "arg2_id": "PMID-8709191_T38", "normalized": [] }, { "id": "PMID-8709191_R9", "type": "Protein-Component", "arg1_id": "PMID-8709191_T17", "arg2_id": "PMID-8709191_T40", "normalized": [] }, { "id": "PMID-8709191_R10", "type": "Protein-Component", "arg1_id": "PMID-8709191_T18", "arg2_id": "PMID-8709191_T45", "normalized": [] } ]

[ { "id": "PMID-10381501__text", "type": "abstract", "text": [ "GATA-1 and erythropoietin cooperate to promote erythroid cell survival by regulating bcl-xL expression. \nThe transcription factor GATA-1 is essential for normal erythropoiesis. By examining in vitro-differentiated embryonic stem cells, we showed previously that in the absence of GATA-1, committed erythroid precursors fail to complete maturation and instead undergo apoptosis. The mechanisms by which GATA-1 controls cell survival are unknown. Here we report that in erythroid cells, GATA-1 strongly induces the expression of the anti-apoptotic protein bcl-xL, but not the related proteins bcl-2 and mcl-1. Consistent with a role for bcl-xL in mediating GATA-1-induced erythroid cell survival, in vitro-differentiated bcl-xL-/- embryonic stem cells fail to generate viable mature definitive erythroid cells, a phenotype resembling that of GATA-1 gene disruption. In addition, we show that erythropoietin, which is also required for erythroid cell survival, cooperates with GATA-1 to stimulate bcl-xL gene expression and to maintain erythroid cell viability during terminal maturation. Together, our data show that bcl-xL is essential for normal erythroid development and suggest a regulatory hierarchy in which bcl-xL is a critical downstream effector of GATA-1 and erythropoietin-mediated signals.\n" ], "offsets": [ [ 0, 1300 ] ] } ]

[ { "id": "PMID-10381501_T1", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 0, 6 ] ], "normalized": [] }, { "id": "PMID-10381501_T2", "type": "Protein", "text": [ "erythropoietin" ], "offsets": [ [ 11, 25 ] ], "normalized": [] }, { "id": "PMID-10381501_T3", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 85, 91 ] ], "normalized": [] }, { "id": "PMID-10381501_T4", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 130, 136 ] ], "normalized": [] }, { "id": "PMID-10381501_T5", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 280, 286 ] ], "normalized": [] }, { "id": "PMID-10381501_T6", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 402, 408 ] ], "normalized": [] }, { "id": "PMID-10381501_T7", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 485, 491 ] ], "normalized": [] }, { "id": "PMID-10381501_T8", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 554, 560 ] ], "normalized": [] }, { "id": "PMID-10381501_T9", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 591, 596 ] ], "normalized": [] }, { "id": "PMID-10381501_T10", "type": "Protein", "text": [ "mcl-1" ], "offsets": [ [ 601, 606 ] ], "normalized": [] }, { "id": "PMID-10381501_T11", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 635, 641 ] ], "normalized": [] }, { "id": "PMID-10381501_T12", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 655, 661 ] ], "normalized": [] }, { "id": "PMID-10381501_T13", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 719, 725 ] ], "normalized": [] }, { "id": "PMID-10381501_T14", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 840, 846 ] ], "normalized": [] }, { "id": "PMID-10381501_T15", "type": "Protein", "text": [ "erythropoietin" ], "offsets": [ [ 890, 904 ] ], "normalized": [] }, { "id": "PMID-10381501_T16", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 974, 980 ] ], "normalized": [] }, { "id": "PMID-10381501_T17", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 994, 1000 ] ], "normalized": [] }, { "id": "PMID-10381501_T18", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 1115, 1121 ] ], "normalized": [] }, { "id": "PMID-10381501_T19", "type": "Protein", "text": [ "bcl-xL" ], "offsets": [ [ 1212, 1218 ] ], "normalized": [] }, { "id": "PMID-10381501_T20", "type": "Protein", "text": [ "GATA-1" ], "offsets": [ [ 1256, 1262 ] ], "normalized": [] }, { "id": "PMID-10381501_T21", "type": "Protein", "text": [ "erythropoietin" ], "offsets": [ [ 1267, 1281 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-7585505__text", "type": "abstract", "text": [ "The normal cell cycle activation program is exploited during the infection of quiescent B lymphocytes by Epstein-Barr virus. \nB lymphocytes in the peripheral circulation are maintained in a non-proliferative state. Antigen recognition stimulates limited proliferation, whereas infection with Epstein-Barr virus (EBV) results in continual proliferation and the outgrowth of immortal cell lines. Because it is not clear at which point in cell cycle the peripheral B lymphocytes are arrested, we characterized the expression of several cell cycle-associated genes in quiescent and stimulated cells. We show that the expression of four cell genes, cdc-2, cyclin E, CD23, and cyclin D2, are up-regulated approximately 100-fold as a result of EBV-mediated immortalization. Because these genes play a positive role in cell proliferation, we suggest that this regulatory switch contributes to controlling entry into the cell cycle. Transient stimulation of quiescent B lymphocytes with either a cocktail of anti-CD40, anti-IgM, and IL4, or EBV results in the rapid expression of the same four genes, suggesting that, after infection, EBV exploits the normal program of B-lymphocyte cell cycle activation.\n" ], "offsets": [ [ 0, 1197 ] ] } ]

[ { "id": "PMID-7585505_T1", "type": "Protein", "text": [ "cdc-2" ], "offsets": [ [ 644, 649 ] ], "normalized": [] }, { "id": "PMID-7585505_T2", "type": "Protein", "text": [ "cyclin E" ], "offsets": [ [ 651, 659 ] ], "normalized": [] }, { "id": "PMID-7585505_T3", "type": "Protein", "text": [ "CD23" ], "offsets": [ [ 661, 665 ] ], "normalized": [] }, { "id": "PMID-7585505_T4", "type": "Protein", "text": [ "cyclin D2" ], "offsets": [ [ 671, 680 ] ], "normalized": [] }, { "id": "PMID-7585505_T5", "type": "Protein", "text": [ "CD40" ], "offsets": [ [ 1004, 1008 ] ], "normalized": [] }, { "id": "PMID-7585505_T6", "type": "Protein", "text": [ "IL4" ], "offsets": [ [ 1024, 1027 ] ], "normalized": [] }, { "id": "PMID-7585505_T7", "type": "Entity", "text": [ "cell cycle-associated genes" ], "offsets": [ [ 533, 560 ] ], "normalized": [] }, { "id": "PMID-7585505_T8", "type": "Entity", "text": [ "cell genes" ], "offsets": [ [ 632, 642 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-1676267__text", "type": "abstract", "text": [ "Towards a molecular understanding of T-cell differentiation. \nLymphoid differentiation is one of the best studied examples of mammalian development. Here Hans Clevers and Michael Owen describe how the cloning of the genes that encode T-cell-specific membrane proteins allows the identification of transcription factors that control the expression of these T-cell genes. Such transcription factors play a key role in the development of the mature T-cell phenotype by functioning as 'master regulators of T-cell differentiation'.\n" ], "offsets": [ [ 0, 528 ] ] } ]

[ { "id": "PMID-1676267_T1", "type": "Entity", "text": [ "T-cell genes" ], "offsets": [ [ 356, 368 ] ], "normalized": [] } ]

[]

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[]

[ { "id": "PMID-8419337__text", "type": "abstract", "text": [ "Involvement of Alu sequences in the cell-specific regulation of transcription of the gamma chain of Fc and T cell receptors. \nThe Fc epsilon RI-gamma chains are expressed in a variety of hematopoietic cells where they play a critical role in signal transduction. They are part of the high affinity IgE receptor in mast cells, basophils, Langerhans cells, and possibly other cells; a component of the low affinity receptor for IgG (Fc gamma RIIIA or CD16) in natural killer cells and macrophages; and part of the T cell antigen receptor in subsets of T cells. Here we have investigated the transcriptional regulation of the gamma chain gene by analyzing the 2.5-kilobase sequence upstream of the transcription start site. This sequence contains a promoter specific to cells of hematopoietic lineage. However, the tissue specificity of this promoter is only partial because it is active in all of the hematopoietic cells tested here, regardless of whether they constitutively express Fc epsilon RI- gamma chain transcripts. We have identified two adjacent cis-acting regulatory elements, both of which are part of an Alu repeat. The first (-445/-366) is a positive element active in both basophils and T cells. The second (-365/-264) binds to nuclear factors, which appear to be different in basophils and T cells, and acts as a negative element in basophils and as a positive one in T cells. Thus, this Alu repeat (90% identical to Alu consensus sequences) has evolved to become both a positive and negative regulator.\n" ], "offsets": [ [ 0, 1518 ] ] } ]

[ { "id": "PMID-8419337_T1", "type": "Protein", "text": [ "Fc epsilon RI-gamma chains" ], "offsets": [ [ 130, 156 ] ], "normalized": [] }, { "id": "PMID-8419337_T2", "type": "Protein", "text": [ "Fc gamma RIIIA" ], "offsets": [ [ 431, 445 ] ], "normalized": [] }, { "id": "PMID-8419337_T3", "type": "Protein", "text": [ "CD16" ], "offsets": [ [ 449, 453 ] ], "normalized": [] }, { "id": "PMID-8419337_T4", "type": "Protein", "text": [ "Fc epsilon RI- gamma chain" ], "offsets": [ [ 982, 1008 ] ], "normalized": [] }, { "id": "PMID-8419337_T5", "type": "Entity", "text": [ "Alu sequences" ], "offsets": [ [ 15, 28 ] ], "normalized": [] }, { "id": "PMID-8419337_T6", "type": "Entity", "text": [ "high affinity IgE receptor" ], "offsets": [ [ 284, 310 ] ], "normalized": [] }, { "id": "PMID-8419337_T7", "type": "Entity", "text": [ "low affinity receptor for IgG" ], "offsets": [ [ 400, 429 ] ], "normalized": [] }, { "id": "PMID-8419337_T8", "type": "Entity", "text": [ "gamma chain gene" ], "offsets": [ [ 623, 639 ] ], "normalized": [] }, { "id": "PMID-8419337_T9", "type": "Entity", "text": [ "2.5-kilobase sequence" ], "offsets": [ [ 657, 678 ] ], "normalized": [] }, { "id": "PMID-8419337_T10", "type": "Entity", "text": [ "transcription start site" ], "offsets": [ [ 695, 719 ] ], "normalized": [] }, { "id": "PMID-8419337_T11", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 746, 754 ] ], "normalized": [] }, { "id": "PMID-8419337_T12", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 839, 847 ] ], "normalized": [] }, { "id": "PMID-8419337_T13", "type": "Entity", "text": [ "cis-acting regulatory elements" ], "offsets": [ [ 1054, 1084 ] ], "normalized": [] }, { "id": "PMID-8419337_T14", "type": "Entity", "text": [ "Alu repeat" ], "offsets": [ [ 1115, 1125 ] ], "normalized": [] }, { "id": "PMID-8419337_T15", "type": "Entity", "text": [ "The first (-445/-366)" ], "offsets": [ [ 1127, 1148 ] ], "normalized": [] }, { "id": "PMID-8419337_T16", "type": "Entity", "text": [ "The second (-365/-264)" ], "offsets": [ [ 1209, 1231 ] ], "normalized": [] }, { "id": "PMID-8419337_T17", "type": "Entity", "text": [ "Alu repeat" ], "offsets": [ [ 1402, 1412 ] ], "normalized": [] }, { "id": "PMID-8419337_T18", "type": "Entity", "text": [ "Alu consensus sequences" ], "offsets": [ [ 1431, 1454 ] ], "normalized": [] }, { "id": "PMID-8419337_T19", "type": "Entity", "text": [ "regulator" ], "offsets": [ [ 1507, 1516 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-8419337_R1", "type": "Subunit-Complex", "arg1_id": "PMID-8419337_T2", "arg2_id": "PMID-8419337_T7", "normalized": [] }, { "id": "PMID-8419337_R2", "type": "Subunit-Complex", "arg1_id": "PMID-8419337_T3", "arg2_id": "PMID-8419337_T7", "normalized": [] } ]

[ { "id": "PMID-9116279__text", "type": "abstract", "text": [ "Lineage- and stage-specific expression of runt box polypeptides in primitive and definitive hematopoiesis. \nTranslocations involving the human CBFA2 locus have been associated with leukemia. This gene, originally named AML1, is a human homologue of the Drosophila gene runt that controls early events in fly embryogenesis. To clarify the role of mammalian runt products in normal and leukemic hematopoiesis, we have studied their pattern of expression in mouse hematopoietic tissues in the adult and during ontogeny using an anti-runt box antiserum. In the adult bone marrow, we found expression of runt polypeptides in differentiating myeloid cells and in B lymphocytes. Within the erythroid lineage, runt expression is biphasic, clearly present in the erythroblasts of early blood islands and of the fetal liver, but absent in the adult. Biochemical analysis by Western blotting of fetal and adult hematopoietic populations shows several runt isoforms. At least one of them appears to be myeloid specific.\n" ], "offsets": [ [ 0, 1008 ] ] } ]

[ { "id": "PMID-9116279_T1", "type": "Protein", "text": [ "runt" ], "offsets": [ [ 42, 46 ] ], "normalized": [] }, { "id": "PMID-9116279_T2", "type": "Protein", "text": [ "CBFA2" ], "offsets": [ [ 143, 148 ] ], "normalized": [] }, { "id": "PMID-9116279_T3", "type": "Protein", "text": [ "AML1" ], "offsets": [ [ 219, 223 ] ], "normalized": [] }, { "id": "PMID-9116279_T4", "type": "Protein", "text": [ "runt" ], "offsets": [ [ 269, 273 ] ], "normalized": [] }, { "id": "PMID-9116279_T5", "type": "Protein", "text": [ "runt" ], "offsets": [ [ 356, 360 ] ], "normalized": [] }, { "id": "PMID-9116279_T6", "type": "Protein", "text": [ "runt" ], "offsets": [ [ 702, 706 ] ], "normalized": [] }, { "id": "PMID-9116279_T7", "type": "Entity", "text": [ "box polypeptides" ], "offsets": [ [ 47, 63 ] ], "normalized": [] }, { "id": "PMID-9116279_T8", "type": "Entity", "text": [ "locus" ], "offsets": [ [ 149, 154 ] ], "normalized": [] }, { "id": "PMID-9116279_T9", "type": "Entity", "text": [ "Drosophila gene runt" ], "offsets": [ [ 253, 273 ] ], "normalized": [] }, { "id": "PMID-9116279_T10", "type": "Entity", "text": [ "runt box" ], "offsets": [ [ 530, 538 ] ], "normalized": [] }, { "id": "PMID-9116279_T11", "type": "Entity", "text": [ "runt polypeptides" ], "offsets": [ [ 599, 616 ] ], "normalized": [] } ]

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[]

[]

[ { "id": "PMID-8707445__text", "type": "abstract", "text": [ "Cytokine-modulating activity of tepoxalin, a new potential antirheumatic. \nTepoxalin is a new dual cyclooxygenase/5-lipoxygenase anti-inflammatory compound currently under clinical investigation. It has been shown to possess anti-inflammatory activity in a variety of animal models and more recently to inhibit IL-2 induced signal transduction. The current study was conducted to evaluate the cytokine modulating activity of tepoxalin and the role of iron in these effects. In human peripheral blood mononuclear cells (PBMC) stimulated with OKT3/PMA, tepoxalin inhibited lymphocyte proliferation with an IC50 of 6 microM. Additionally, it inhibited the production of LTB4 (IC50 = 0.5 microM) and the cytokines IL-2, IL-6 and TNF alpha (IC50 = 10-12 microM). Cytotoxicity was not demonstrated at these concentrations. Add-back experiments with either cytokines (IL-2 or IL-6), LTB4 or conditioned media failed to restore the proliferative response in the presence of tepoxalin. However, the concurrent addition of iron (in the form of ferrous or ferric chloride and other iron salts) reversed the inhibition of proliferation caused by tepoxalin. Tepoxalin also inhibits the activation of NF kappa B, a transcription factor which acts on several cytokine genes. Tepoxalin's effect on NF kappa B is also reversed by the addition of iron salts. These data suggest that the action of tepoxalin to inhibit proliferation in PBMC may be at least in part due to its ability to reduce the amount of available iron resulting in decreased activation of NF kappa B and subsequent inhibition of cytokine production.\n" ], "offsets": [ [ 0, 1602 ] ] } ]

[ { "id": "PMID-8707445_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 311, 315 ] ], "normalized": [] }, { "id": "PMID-8707445_T2", "type": "Protein", "text": [ "LTB4" ], "offsets": [ [ 667, 671 ] ], "normalized": [] }, { "id": "PMID-8707445_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 710, 714 ] ], "normalized": [] }, { "id": "PMID-8707445_T4", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 716, 720 ] ], "normalized": [] }, { "id": "PMID-8707445_T5", "type": "Protein", "text": [ "TNF alpha" ], "offsets": [ [ 725, 734 ] ], "normalized": [] }, { "id": "PMID-8707445_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 861, 865 ] ], "normalized": [] }, { "id": "PMID-8707445_T7", "type": "Protein", "text": [ "IL-6" ], "offsets": [ [ 869, 873 ] ], "normalized": [] }, { "id": "PMID-8707445_T8", "type": "Protein", "text": [ "LTB4" ], "offsets": [ [ 876, 880 ] ], "normalized": [] }, { "id": "PMID-8707445_T9", "type": "Entity", "text": [ "NF kappa B" ], "offsets": [ [ 1187, 1197 ] ], "normalized": [] }, { "id": "PMID-8707445_T10", "type": "Entity", "text": [ "cytokine genes" ], "offsets": [ [ 1244, 1258 ] ], "normalized": [] }, { "id": "PMID-8707445_T11", "type": "Entity", "text": [ "NF kappa B" ], "offsets": [ [ 1282, 1292 ] ], "normalized": [] }, { "id": "PMID-8707445_T12", "type": "Entity", "text": [ "NF kappa B" ], "offsets": [ [ 1541, 1551 ] ], "normalized": [] } ]

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[ { "id": "PMID-9973520__text", "type": "abstract", "text": [ "Cross-linking of CD44 on rheumatoid synovial cells up-regulates VCAM-1. \nCD44 is a ubiquitous molecule also known as hyaluronic acid or homing receptor. However, the cellular functions and its role in inflammation, for example, rheumatoid synovitis, are currently unknown. In this study, we propose a novel function for CD44. Using synovial cells from rheumatoid arthritis (RA) patients, we demonstrated that CD44 cross-linking and binding to hyaluronan augmented VCAM-1 expression and subsequently VCAM-1-mediated cell adhesion. Briefly, we found that 1) rheumatoid synovial cells highly expressed CD44; 2) cross-linking of CD44 markedly but transiently augmented VCAM-1 expression and its mRNA transcription much more than did IL-1beta and TNF-alpha; 3) hyaluronan, especially when fragmented, also up-regulated VCAM-1; 4) CD44 activated the transcription factor AP-1; and 5) the integrin-dependent adhesive function of RA synovial cells to T cells was also amplified by CD44 cross-linking. These results indicate that the adhesion of RA synovial cells to matrices such as hyaluronic acid through CD44 could up-regulate VCAM-1 expression and VCAM-1-mediated adhesion to T cells, which might in turn cause activation of T cells and synovial cells in RA synovitis. We therefore propose that such cross-talking among distinct adhesion molecules may be involved in the pathogenesis of inflammation, including RA synovitis.\n" ], "offsets": [ [ 0, 1421 ] ] } ]

[ { "id": "PMID-9973520_T1", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 17, 21 ] ], "normalized": [] }, { "id": "PMID-9973520_T2", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 64, 70 ] ], "normalized": [] }, { "id": "PMID-9973520_T3", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 73, 77 ] ], "normalized": [] }, { "id": "PMID-9973520_T4", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 320, 324 ] ], "normalized": [] }, { "id": "PMID-9973520_T5", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 409, 413 ] ], "normalized": [] }, { "id": "PMID-9973520_T6", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 464, 470 ] ], "normalized": [] }, { "id": "PMID-9973520_T7", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 499, 505 ] ], "normalized": [] }, { "id": "PMID-9973520_T8", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 599, 603 ] ], "normalized": [] }, { "id": "PMID-9973520_T9", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 625, 629 ] ], "normalized": [] }, { "id": "PMID-9973520_T10", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 665, 671 ] ], "normalized": [] }, { "id": "PMID-9973520_T11", "type": "Protein", "text": [ "IL-1beta" ], "offsets": [ [ 729, 737 ] ], "normalized": [] }, { "id": "PMID-9973520_T12", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 742, 751 ] ], "normalized": [] }, { "id": "PMID-9973520_T13", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 814, 820 ] ], "normalized": [] }, { "id": "PMID-9973520_T14", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 825, 829 ] ], "normalized": [] }, { "id": "PMID-9973520_T15", "type": "Protein", "text": [ "AP-1" ], "offsets": [ [ 865, 869 ] ], "normalized": [] }, { "id": "PMID-9973520_T16", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 973, 977 ] ], "normalized": [] }, { "id": "PMID-9973520_T17", "type": "Protein", "text": [ "CD44" ], "offsets": [ [ 1099, 1103 ] ], "normalized": [] }, { "id": "PMID-9973520_T18", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1122, 1128 ] ], "normalized": [] }, { "id": "PMID-9973520_T19", "type": "Protein", "text": [ "VCAM-1" ], "offsets": [ [ 1144, 1150 ] ], "normalized": [] }, { "id": "PMID-9973520_T20", "type": "Entity", "text": [ "mRNA" ], "offsets": [ [ 691, 695 ] ], "normalized": [] } ]

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[ { "id": "PMID-8790371__text", "type": "abstract", "text": [ "Apoptosis mediated by HIV protease is preceded by cleavage of Bcl-2. \nExpression of the human immunodeficiency virus type 1 (HIV) protease in cultured cells leads to apoptosis, preceded by cleavage of bcl-2, a key negative regulator of cell death. In contrast, a high level of bcl-2 protects cells in vitro and in vivo from the viral protease and prevents cell death following HIV infection of human lymphocytes, while reducing the yields of viral structural proteins, infectivity, and tumor necrosis factor alpha. We present a model for HIV replication in which the viral protease depletes the infected cells of bcl-2, leading to oxidative stress-dependent activation of NF kappa B, a cellular factor required for HIV transcription, and ultimately to cell death. Purified bcl-2 is cleaved by HIV protease between phenylalanine 112 and alanine 113. The results suggest a new option for HIV gene therapy; bcl-2 muteins that have noncleavable alterations surrounding the HIV protease cleavage site.\n" ], "offsets": [ [ 0, 997 ] ] } ]

[ { "id": "PMID-8790371_T1", "type": "Protein", "text": [ "HIV protease" ], "offsets": [ [ 22, 34 ] ], "normalized": [] }, { "id": "PMID-8790371_T2", "type": "Protein", "text": [ "Bcl-2" ], "offsets": [ [ 62, 67 ] ], "normalized": [] }, { "id": "PMID-8790371_T3", "type": "Protein", "text": [ "human immunodeficiency virus type 1 (HIV) protease" ], "offsets": [ [ 88, 138 ] ], "normalized": [] }, { "id": "PMID-8790371_T4", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 201, 206 ] ], "normalized": [] }, { "id": "PMID-8790371_T5", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 277, 282 ] ], "normalized": [] }, { "id": "PMID-8790371_T6", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 486, 513 ] ], "normalized": [] }, { "id": "PMID-8790371_T7", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 613, 618 ] ], "normalized": [] }, { "id": "PMID-8790371_T8", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 773, 778 ] ], "normalized": [] }, { "id": "PMID-8790371_T9", "type": "Protein", "text": [ "HIV protease" ], "offsets": [ [ 793, 805 ] ], "normalized": [] }, { "id": "PMID-8790371_T10", "type": "Protein", "text": [ "bcl-2" ], "offsets": [ [ 904, 909 ] ], "normalized": [] }, { "id": "PMID-8790371_T11", "type": "Protein", "text": [ "HIV protease" ], "offsets": [ [ 969, 981 ] ], "normalized": [] }, { "id": "PMID-8790371_T12", "type": "Entity", "text": [ "NF kappa B" ], "offsets": [ [ 672, 682 ] ], "normalized": [] }, { "id": "PMID-8790371_T13", "type": "Entity", "text": [ "phenylalanine 112" ], "offsets": [ [ 814, 831 ] ], "normalized": [] }, { "id": "PMID-8790371_T14", "type": "Entity", "text": [ "alanine 113" ], "offsets": [ [ 836, 847 ] ], "normalized": [] }, { "id": "PMID-8790371_T15", "type": "Entity", "text": [ "noncleavable alterations" ], "offsets": [ [ 928, 952 ] ], "normalized": [] }, { "id": "PMID-8790371_T16", "type": "Entity", "text": [ "cleavage site" ], "offsets": [ [ 982, 995 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-8790371_R1", "type": "Protein-Component", "arg1_id": "PMID-8790371_T10", "arg2_id": "PMID-8790371_T16", "normalized": [] }, { "id": "PMID-8790371_R2", "type": "Protein-Component", "arg1_id": "PMID-8790371_T10", "arg2_id": "PMID-8790371_T15", "normalized": [] } ]

[ { "id": "PMID-9218843__text", "type": "abstract", "text": [ "Rescue by cytokines of apoptotic cell death induced by IL-2 deprivation of human antigen-specific T cell clones. \nThe control of cell survival and cell death is of central importance in tissues with high cell turnover such as the lymphoid system. We have examined the effect of cytokines on IL-2 deprivation-induced apoptosis of human antigen-specific T helper clones with different cytokine production profiles. We found that IL-2, interferon-alpha (IFN-alpha), and IFN-beta inhibited IL-2 deprivation apoptosis in Th0, Th1, and Th2 clones. We also found that IL-2 protects T cell clones from IL-2 deprivation apoptosis accompanying active proliferation and enhanced expression of P53, Rb and Bcl-xL proteins. In contrast, IFN-alpha/beta rescued T cell clones from apoptosis without active proliferation, and expression of apoptosis-associated proteins tested so far was unaffected. This may be due to the fact that T cells treated with IL-2 contained those located in S + G2/M phases of the cell cycle, whereas the vast majority of T cells treated with IFN-alpha/beta were located in G0/G1 phase. IFN-alpha/beta specifically induced tyrosine phosphorylation and translocation into nucleus of signal transducers and activators of transcription (STAT) 2 protein in the T cell clones. In addition, over-expression of STAT2 by transfection of the cDNA prevented apoptosis of the T cell clones. Our present study shows that IFN-alpha and -beta mediate anti-apoptotic effect through other pathways than that of IL-2 in growth factor deprivation apoptosis.\n" ], "offsets": [ [ 0, 1552 ] ] } ]

[ { "id": "PMID-9218843_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 55, 59 ] ], "normalized": [] }, { "id": "PMID-9218843_T2", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 291, 295 ] ], "normalized": [] }, { "id": "PMID-9218843_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 427, 431 ] ], "normalized": [] }, { "id": "PMID-9218843_T4", "type": "Protein", "text": [ "IFN-beta" ], "offsets": [ [ 467, 475 ] ], "normalized": [] }, { "id": "PMID-9218843_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 486, 490 ] ], "normalized": [] }, { "id": "PMID-9218843_T6", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 561, 565 ] ], "normalized": [] }, { "id": "PMID-9218843_T7", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 594, 598 ] ], "normalized": [] }, { "id": "PMID-9218843_T8", "type": "Protein", "text": [ "P53" ], "offsets": [ [ 682, 685 ] ], "normalized": [] }, { "id": "PMID-9218843_T9", "type": "Protein", "text": [ "Rb" ], "offsets": [ [ 687, 689 ] ], "normalized": [] }, { "id": "PMID-9218843_T10", "type": "Protein", "text": [ "Bcl-xL" ], "offsets": [ [ 694, 700 ] ], "normalized": [] }, { "id": "PMID-9218843_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 938, 942 ] ], "normalized": [] }, { "id": "PMID-9218843_T12", "type": "Protein", "text": [ "signal transducers and activators of transcription (STAT) 2" ], "offsets": [ [ 1194, 1253 ] ], "normalized": [] }, { "id": "PMID-9218843_T13", "type": "Protein", "text": [ "STAT2" ], "offsets": [ [ 1316, 1321 ] ], "normalized": [] }, { "id": "PMID-9218843_T14", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 1507, 1511 ] ], "normalized": [] }, { "id": "PMID-9218843_T15", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 1135, 1143 ] ], "normalized": [] } ]

[]

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[ { "id": "PMID-9237716__text", "type": "abstract", "text": [ "Induction of human immunodeficiency virus type 1 expression in monocytic cells by Cryptococcus neoformans and Candida albicans. \nBecause candidiasis and cryptococcosis are common in human immunodeficiency virus (HIV)-infected persons, the effect of Cryptococcus neoformans and Candida albicans on HIV expression in monocytic cells was examined. Stimulation of the latently HIV-infected myelomonocytic cell line OM-10.1 with C. neoformans and C. albicans in the presence of pooled human serum caused a ratio-dependent increase in HIV production. Induction of HIV by C. neoformans was enhanced by anti-capsular antibody, while induction by both organisms was inhibited by anti-TNF-alpha antibody. In THP-1 cells transfected with HIV plasmid constructs, both organisms induced transcription from the HIV long terminal repeat that was dependent on intact NF-kappaB binding sequences. Thus, C. neoformans and C. albicans enhance HIV expression in monocytic cells through a TNF-alpha- and NF-kappaB-dependent mechanism. In HIV-infected patients, such enhancement may further impair host immunity and could accelerate the course of HIV disease.\n" ], "offsets": [ [ 0, 1138 ] ] } ]

[ { "id": "PMID-9237716_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 675, 684 ] ], "normalized": [] }, { "id": "PMID-9237716_T2", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 968, 977 ] ], "normalized": [] }, { "id": "PMID-9237716_T3", "type": "Entity", "text": [ "HIV plasmid constructs" ], "offsets": [ [ 727, 749 ] ], "normalized": [] }, { "id": "PMID-9237716_T4", "type": "Entity", "text": [ "HIV long terminal repeat" ], "offsets": [ [ 797, 821 ] ], "normalized": [] }, { "id": "PMID-9237716_T5", "type": "Entity", "text": [ "NF-kappaB binding sequences" ], "offsets": [ [ 851, 878 ] ], "normalized": [] }, { "id": "PMID-9237716_T6", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 851, 860 ] ], "normalized": [] }, { "id": "PMID-9237716_T7", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 983, 992 ] ], "normalized": [] } ]

[]

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[]

[ { "id": "PMID-7641692__text", "type": "abstract", "text": [ "IL-2 gene expression and NF-kappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase. \nActivation of the CD28 surface receptor provides a major costimulatory signal for T cell activation resulting in enhanced production of interleukin-2 (IL-2) and cell proliferation. In primary T lymphocytes we show that CD28 ligation leads to the rapid intracellular formation of reactive oxygen intermediates (ROIs) which are required for CD28-mediated activation of the NF-kappa B/CD28-responsive complex and IL-2 expression. Delineation of the CD28 signaling cascade was found to involve protein tyrosine kinase activity, followed by the activation of phospholipase A2 and 5-lipoxygenase. Our data suggest that lipoxygenase metabolites activate ROI formation which then induce IL-2 expression via NF-kappa B activation. These findings should be useful for therapeutic strategies and the development of immunosuppressants targeting the CD28 costimulatory pathway.\n" ], "offsets": [ [ 0, 981 ] ] } ]

[ { "id": "PMID-7641692_T1", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 0, 4 ] ], "normalized": [] }, { "id": "PMID-7641692_T2", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 55, 59 ] ], "normalized": [] }, { "id": "PMID-7641692_T3", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 134, 138 ] ], "normalized": [] }, { "id": "PMID-7641692_T4", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 252, 265 ] ], "normalized": [] }, { "id": "PMID-7641692_T5", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 267, 271 ] ], "normalized": [] }, { "id": "PMID-7641692_T6", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 335, 339 ] ], "normalized": [] }, { "id": "PMID-7641692_T7", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 455, 459 ] ], "normalized": [] }, { "id": "PMID-7641692_T8", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 498, 502 ] ], "normalized": [] }, { "id": "PMID-7641692_T9", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 526, 530 ] ], "normalized": [] }, { "id": "PMID-7641692_T10", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 562, 566 ] ], "normalized": [] }, { "id": "PMID-7641692_T11", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 795, 799 ] ], "normalized": [] }, { "id": "PMID-7641692_T12", "type": "Protein", "text": [ "CD28" ], "offsets": [ [ 953, 957 ] ], "normalized": [] }, { "id": "PMID-7641692_T13", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 25, 35 ] ], "normalized": [] }, { "id": "PMID-7641692_T14", "type": "Entity", "text": [ "NF-kappa B/CD28-responsive complex" ], "offsets": [ [ 487, 521 ] ], "normalized": [] }, { "id": "PMID-7641692_T15", "type": "Entity", "text": [ "CD28-responsive complex" ], "offsets": [ [ 498, 521 ] ], "normalized": [] }, { "id": "PMID-7641692_T16", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 815, 825 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-7641692_1", "entity_ids": [ "PMID-7641692_T4", "PMID-7641692_T5" ] } ]

[]

[ { "id": "PMID-10224109__text", "type": "abstract", "text": [ "Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. \nPG490 (triptolide) is a diterpene triepoxide with potent immunosuppressive and antiinflammatory properties. PG490 inhibits interleukin(IL)-2 expression by normal human peripheral blood lymphocytes stimulated with phorbol 12-myristate 13-acetate (PMA) and antibody to CD3 (IC50 of 10 ng/ml), and with PMA and ionomycin (Iono, IC50 of 40 ng/ml). In Jurkat T-cells, PG490 inhibits PMA/Iono-stimulated IL-2 transcription. PG490 inhibits the induction of DNA binding activity at the purine-box/antigen receptor response element (ARRE)/nuclear factor of activated T-cells (NF-AT) target sequence but not at the NF-kappaB site. PG490 can completely inhibit transcriptional activation at the purine-box/ARRE/NF-AT and NF-kappaB target DNA sequences triggered by all stimuli examined (PMA, PMA/Iono, tumor necrosis factor-alpha). PG490 also inhibits PMA-stimulated activation of a chimeric transcription factor in which the C-terminal TA1 transactivation domain of NF-kappaB p65 is fused to the DNA binding domain of GAL4. In 16HBE human bronchial epithelial cells, IL-8 expression is regulated predominantly by NF-kappaB, and PG490 but not cyclosporin A can completely inhibit expression of IL-8. The mechanism of PG490 inhibition of cytokine gene expression differs from cyclosporin A and involves nuclear inhibition of transcriptional activation of NF-kappaB and the purine-box regulator operating at the ARRE/NF-AT site at a step after specific DNA binding.\n" ], "offsets": [ [ 0, 1637 ] ] } ]

[ { "id": "PMID-10224109_T1", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 53, 66 ] ], "normalized": [] }, { "id": "PMID-10224109_T2", "type": "Protein", "text": [ "interleukin(IL)-2" ], "offsets": [ [ 307, 324 ] ], "normalized": [] }, { "id": "PMID-10224109_T3", "type": "Protein", "text": [ "IL-2" ], "offsets": [ [ 582, 586 ] ], "normalized": [] }, { "id": "PMID-10224109_T4", "type": "Protein", "text": [ "tumor necrosis factor-alpha" ], "offsets": [ [ 975, 1002 ] ], "normalized": [] }, { "id": "PMID-10224109_T5", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 1150, 1153 ] ], "normalized": [] }, { "id": "PMID-10224109_T6", "type": "Protein", "text": [ "GAL4" ], "offsets": [ [ 1192, 1196 ] ], "normalized": [] }, { "id": "PMID-10224109_T7", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1241, 1245 ] ], "normalized": [] }, { "id": "PMID-10224109_T8", "type": "Protein", "text": [ "IL-8" ], "offsets": [ [ 1367, 1371 ] ], "normalized": [] }, { "id": "PMID-10224109_T9", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 145, 154 ] ], "normalized": [] }, { "id": "PMID-10224109_T10", "type": "Entity", "text": [ "CD3" ], "offsets": [ [ 451, 454 ] ], "normalized": [] }, { "id": "PMID-10224109_T11", "type": "Entity", "text": [ "purine-box/antigen receptor response element (ARRE)/nuclear factor of activated T-cells (NF-AT) target sequence" ], "offsets": [ [ 662, 773 ] ], "normalized": [] }, { "id": "PMID-10224109_T12", "type": "Entity", "text": [ "NF-kappaB site" ], "offsets": [ [ 789, 803 ] ], "normalized": [] }, { "id": "PMID-10224109_T13", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 789, 798 ] ], "normalized": [] }, { "id": "PMID-10224109_T14", "type": "Entity", "text": [ "target DNA sequences" ], "offsets": [ [ 904, 924 ] ], "normalized": [] }, { "id": "PMID-10224109_T15", "type": "Entity", "text": [ "C-terminal TA1 transactivation domain" ], "offsets": [ [ 1099, 1136 ] ], "normalized": [] }, { "id": "PMID-10224109_T16", "type": "Entity", "text": [ "DNA binding domain" ], "offsets": [ [ 1170, 1188 ] ], "normalized": [] }, { "id": "PMID-10224109_T17", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1287, 1296 ] ], "normalized": [] }, { "id": "PMID-10224109_T18", "type": "Entity", "text": [ "cytokine gene" ], "offsets": [ [ 1410, 1423 ] ], "normalized": [] }, { "id": "PMID-10224109_T19", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1527, 1536 ] ], "normalized": [] }, { "id": "PMID-10224109_T20", "type": "Entity", "text": [ "purine-box regulator" ], "offsets": [ [ 1545, 1565 ] ], "normalized": [] }, { "id": "PMID-10224109_T21", "type": "Entity", "text": [ "ARRE/NF-AT site" ], "offsets": [ [ 1583, 1598 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-10224109_R1", "type": "Protein-Component", "arg1_id": "PMID-10224109_T6", "arg2_id": "PMID-10224109_T16", "normalized": [] }, { "id": "PMID-10224109_R2", "type": "Protein-Component", "arg1_id": "PMID-10224109_T5", "arg2_id": "PMID-10224109_T15", "normalized": [] } ]

[ { "id": "PMID-8663174__text", "type": "abstract", "text": [ "Multiple transcription factors are required for activation of human interleukin 9 gene in T cells. \nThe genetic elements and regulatory mechanisms responsible for human interleukin 9 (IL-9) gene expression in a human T cell leukemia virus type I-transformed human T cell line, C5MJ2, were investigated. We demonstrated that IL-9 gene expression is controlled, at least in part, by transcriptional activation. Transient expression of the luciferase reporter gene linked to serially deleted sequences of the 5'-flanking region of the IL-9 gene has revealed several positive and negative regulatory elements involved in the basal and inducible expression of the IL-9 gene in C5MJ2 cells. An AP-1 site at -146 to -140 was shown to be involved in the expression of the IL-9 gene. A proximal region between -46 and -80 was identified as the minimum sequence for the basal and inducible expression of the IL-9 gene in C5MJ2 cells. Within this region, an NF-kappaB site at -59 to -50 and its adjacent 20-base pair upstream sequence were demonstrated to play a critical role for the IL-9 promoter activity. DNA-protein binding studies indicated that NF-kappaB, c-Jun, and potentially novel proteins (around 35 kDa) can bind to this important sequence. Mutations at different sites within this proximal promoter region abolished the promoter activity as well as the DNA binding. Taken together, these results suggest that the cooperation of different transcription factors is essential for IL-9 gene expression in T cells.\n" ], "offsets": [ [ 0, 1513 ] ] } ]

[ { "id": "PMID-8663174_T1", "type": "Protein", "text": [ "interleukin 9" ], "offsets": [ [ 68, 81 ] ], "normalized": [] }, { "id": "PMID-8663174_T2", "type": "Protein", "text": [ "interleukin 9" ], "offsets": [ [ 169, 182 ] ], "normalized": [] }, { "id": "PMID-8663174_T3", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 184, 188 ] ], "normalized": [] }, { "id": "PMID-8663174_T4", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 324, 328 ] ], "normalized": [] }, { "id": "PMID-8663174_T5", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 532, 536 ] ], "normalized": [] }, { "id": "PMID-8663174_T6", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 659, 663 ] ], "normalized": [] }, { "id": "PMID-8663174_T7", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 764, 768 ] ], "normalized": [] }, { "id": "PMID-8663174_T8", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 898, 902 ] ], "normalized": [] }, { "id": "PMID-8663174_T9", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 1074, 1078 ] ], "normalized": [] }, { "id": "PMID-8663174_T10", "type": "Protein", "text": [ "c-Jun" ], "offsets": [ [ 1152, 1157 ] ], "normalized": [] }, { "id": "PMID-8663174_T11", "type": "Protein", "text": [ "IL-9" ], "offsets": [ [ 1480, 1484 ] ], "normalized": [] }, { "id": "PMID-8663174_T12", "type": "Entity", "text": [ "luciferase reporter gene" ], "offsets": [ [ 437, 461 ] ], "normalized": [] }, { "id": "PMID-8663174_T13", "type": "Entity", "text": [ "5'-flanking region" ], "offsets": [ [ 506, 524 ] ], "normalized": [] }, { "id": "PMID-8663174_T14", "type": "Entity", "text": [ "regulatory elements" ], "offsets": [ [ 585, 604 ] ], "normalized": [] }, { "id": "PMID-8663174_T15", "type": "Entity", "text": [ "AP-1 site" ], "offsets": [ [ 688, 697 ] ], "normalized": [] }, { "id": "PMID-8663174_T16", "type": "Entity", "text": [ "AP-1" ], "offsets": [ [ 688, 692 ] ], "normalized": [] }, { "id": "PMID-8663174_T17", "type": "Entity", "text": [ "-146 to -140" ], "offsets": [ [ 701, 713 ] ], "normalized": [] }, { "id": "PMID-8663174_T18", "type": "Entity", "text": [ "proximal region" ], "offsets": [ [ 777, 792 ] ], "normalized": [] }, { "id": "PMID-8663174_T19", "type": "Entity", "text": [ "-46 and -80" ], "offsets": [ [ 801, 812 ] ], "normalized": [] }, { "id": "PMID-8663174_T20", "type": "Entity", "text": [ "NF-kappaB site" ], "offsets": [ [ 947, 961 ] ], "normalized": [] }, { "id": "PMID-8663174_T21", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 947, 956 ] ], "normalized": [] }, { "id": "PMID-8663174_T22", "type": "Entity", "text": [ "-59 to -50" ], "offsets": [ [ 965, 975 ] ], "normalized": [] }, { "id": "PMID-8663174_T23", "type": "Entity", "text": [ "20-base pair upstream sequence" ], "offsets": [ [ 993, 1023 ] ], "normalized": [] }, { "id": "PMID-8663174_T24", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1079, 1087 ] ], "normalized": [] }, { "id": "PMID-8663174_T25", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1141, 1150 ] ], "normalized": [] }, { "id": "PMID-8663174_T26", "type": "Entity", "text": [ "proximal promoter region" ], "offsets": [ [ 1284, 1308 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-8663174_1", "entity_ids": [ "PMID-8663174_T2", "PMID-8663174_T3" ] } ]

[ { "id": "PMID-8663174_R1", "type": "Protein-Component", "arg1_id": "PMID-8663174_T5", "arg2_id": "PMID-8663174_T13", "normalized": [] }, { "id": "PMID-8663174_R2", "type": "Protein-Component", "arg1_id": "PMID-8663174_T6", "arg2_id": "PMID-8663174_T14", "normalized": [] }, { "id": "PMID-8663174_R3", "type": "Protein-Component", "arg1_id": "PMID-8663174_T5", "arg2_id": "PMID-8663174_T14", "normalized": [] }, { "id": "PMID-8663174_R4", "type": "Protein-Component", "arg1_id": "PMID-8663174_T9", "arg2_id": "PMID-8663174_T24", "normalized": [] } ]

[ { "id": "PMID-9838061__text", "type": "abstract", "text": [ "Anaphylatoxins C5a and C3a induce nuclear factor kappaB activation in human peripheral blood monocytes. \nThe anaphylatoxins C5a and C3a are involved in the regulation of cytokine production. In this study the capability of C5a and C3a to induce transcription factor activation was examined. C5a and C3a stimulation of human peripheral blood monocytes resulted in nuclear expression of a DNA binding activity with specificity to the kappaB sequence. The p50 and p65 proteins, constituents of the prototypic nuclear factor kappaB, were identified as components of the DNA-protein complexes by anti-peptide antibodies in gel supershift assays. C5a induced kappaB binding activity was detected 15 min after agonist stimulation, peaked at 30-40 min, and remained detectable at 2 h. Binding to kappaB sequence was accompanied by an initial decrease and subsequent increase in the cytoplasmic IkappaBalpha levels, as detected by Western blotting using an anti-IkappaBalpha antibody. Pertussis toxin treatment markedly decreased kappaB binding activities induced by both C5a and C3a, whereas cholera toxin displayed no inhibitory effect. Neither of the two toxins affected kappaB binding activity induced by TNFalpha in the same cells. These results imply a potential role of the anaphylatoxins C5a and C3a in regulating leukocytes gene expression through G protein-coupled transcription factor activation.\n" ], "offsets": [ [ 0, 1399 ] ] } ]

[ { "id": "PMID-9838061_T1", "type": "Protein", "text": [ "C5a" ], "offsets": [ [ 15, 18 ] ], "normalized": [] }, { "id": "PMID-9838061_T2", "type": "Protein", "text": [ "C3a" ], "offsets": [ [ 23, 26 ] ], "normalized": [] }, { "id": "PMID-9838061_T3", "type": "Protein", "text": [ "C5a" ], "offsets": [ [ 124, 127 ] ], "normalized": [] }, { "id": "PMID-9838061_T4", "type": "Protein", "text": [ "C3a" ], "offsets": [ [ 132, 135 ] ], "normalized": [] }, { "id": "PMID-9838061_T5", "type": "Protein", "text": [ "C5a" ], "offsets": [ [ 223, 226 ] ], "normalized": [] }, { "id": "PMID-9838061_T6", "type": "Protein", "text": [ "C3a" ], "offsets": [ [ 231, 234 ] ], "normalized": [] }, { "id": "PMID-9838061_T7", "type": "Protein", "text": [ "C5a" ], "offsets": [ [ 291, 294 ] ], "normalized": [] }, { "id": "PMID-9838061_T8", "type": "Protein", "text": [ "C3a" ], "offsets": [ [ 299, 302 ] ], "normalized": [] }, { "id": "PMID-9838061_T9", "type": "Protein", "text": [ "p50" ], "offsets": [ [ 453, 456 ] ], "normalized": [] }, { "id": "PMID-9838061_T10", "type": "Protein", "text": [ "p65" ], "offsets": [ [ 461, 464 ] ], "normalized": [] }, { "id": "PMID-9838061_T11", "type": "Protein", "text": [ "C5a" ], "offsets": [ [ 641, 644 ] ], "normalized": [] }, { "id": "PMID-9838061_T12", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 886, 898 ] ], "normalized": [] }, { "id": "PMID-9838061_T13", "type": "Protein", "text": [ "IkappaBalpha" ], "offsets": [ [ 953, 965 ] ], "normalized": [] }, { "id": "PMID-9838061_T14", "type": "Protein", "text": [ "C5a" ], "offsets": [ [ 1063, 1066 ] ], "normalized": [] }, { "id": "PMID-9838061_T15", "type": "Protein", "text": [ "C3a" ], "offsets": [ [ 1071, 1074 ] ], "normalized": [] }, { "id": "PMID-9838061_T16", "type": "Protein", "text": [ "TNFalpha" ], "offsets": [ [ 1200, 1208 ] ], "normalized": [] }, { "id": "PMID-9838061_T17", "type": "Protein", "text": [ "C5a" ], "offsets": [ [ 1287, 1290 ] ], "normalized": [] }, { "id": "PMID-9838061_T18", "type": "Protein", "text": [ "C3a" ], "offsets": [ [ 1295, 1298 ] ], "normalized": [] }, { "id": "PMID-9838061_T19", "type": "Entity", "text": [ "nuclear factor kappaB" ], "offsets": [ [ 34, 55 ] ], "normalized": [] }, { "id": "PMID-9838061_T20", "type": "Entity", "text": [ "transcription factor" ], "offsets": [ [ 245, 265 ] ], "normalized": [] }, { "id": "PMID-9838061_T21", "type": "Entity", "text": [ "kappaB sequence" ], "offsets": [ [ 432, 447 ] ], "normalized": [] }, { "id": "PMID-9838061_T22", "type": "Entity", "text": [ "nuclear factor kappaB" ], "offsets": [ [ 506, 527 ] ], "normalized": [] }, { "id": "PMID-9838061_T23", "type": "Entity", "text": [ "DNA-protein complexes" ], "offsets": [ [ 566, 587 ] ], "normalized": [] }, { "id": "PMID-9838061_T24", "type": "Entity", "text": [ "kappaB sequence" ], "offsets": [ [ 788, 803 ] ], "normalized": [] }, { "id": "PMID-9838061_T25", "type": "Entity", "text": [ "Pertussis toxin" ], "offsets": [ [ 976, 991 ] ], "normalized": [] }, { "id": "PMID-9838061_T26", "type": "Entity", "text": [ "kappaB" ], "offsets": [ [ 1021, 1027 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-9838061_R1", "type": "Subunit-Complex", "arg1_id": "PMID-9838061_T9", "arg2_id": "PMID-9838061_T22", "normalized": [] }, { "id": "PMID-9838061_R2", "type": "Subunit-Complex", "arg1_id": "PMID-9838061_T9", "arg2_id": "PMID-9838061_T23", "normalized": [] }, { "id": "PMID-9838061_R3", "type": "Subunit-Complex", "arg1_id": "PMID-9838061_T10", "arg2_id": "PMID-9838061_T22", "normalized": [] }, { "id": "PMID-9838061_R4", "type": "Subunit-Complex", "arg1_id": "PMID-9838061_T10", "arg2_id": "PMID-9838061_T23", "normalized": [] } ]

[ { "id": "PMID-10210645__text", "type": "abstract", "text": [ "LPS-Induced NF-kappaB activation and TNF-alpha release in human monocytes are protein tyrosine kinase dependent and protein kinase C independent. \nBACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is an important mediator of septic shock. Endotoxin (LPS) signal transduction in human monocytes leads to activation of nuclear factor-kappa B (NF-kappaB) and TNF-alpha release. Previous studies have implicated activation of both protein kinase C (PKC) and protein tyrosine kinases (PTK) in LPS-induced NF-kappaB activation and TNF-alpha production. We hypothesized that inhibition of either PKC or PTK would decrease LPS-induced NF-kappaB DNA binding and TNF-alpha release in human monocytes. MATERIALS AND METHODS: Human monocytes were stimulated with PMA (50 ng/ml) alone or LPS (100 ng/ml) with and without a nonspecific serine/threonine protein kinase inhibitor staurosporine (Stauro), a specific pan-PKC inhibitor bisindolylmaleimide (Bis), or an inhibitor of PTK genistein (Gen). TNF-alpha release in culture supernatants was measured by an ELISA. NF-kappaB DNA binding was evaluated by electrophoretic mobility shift assay. RESULTS: LPS increased NF-kappaB DNA binding and TNF-alpha release in human monocytes. Nonspecific protein kinase inhibition inhibited NF-kappaB activation and TNF-alpha release, while specific PKC inhibition with Bis had no effect on LPS-induced NF-kappaB DNA binding or TNF-alpha release. PTK inhibition with Gen attenuated both LPS-induced NF-kappaB DNA binding and TNF-alpha production in human monocytes. Direct activation of PKC with PMA induced both NF-kappaB activation and TNF-alpha production by human monocytes. CONCLUSIONS: These results suggest that LPS-induced NF-kappaB activation and TNF-alpha release in human monocytes are independent of PKC activity. Furthermore, our results provide evidence that PTK plays a role in LPS-induced NF-kappaB activation and TNF-alpha release in human monocytes and thus could be a potential therapeutic target in inflammatory states. Copyright 1999 Academic Press.\n" ], "offsets": [ [ 0, 2046 ] ] } ]

[ { "id": "PMID-10210645_T1", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 37, 46 ] ], "normalized": [] }, { "id": "PMID-10210645_T2", "type": "Protein", "text": [ "Tumor necrosis factor alpha" ], "offsets": [ [ 159, 186 ] ], "normalized": [] }, { "id": "PMID-10210645_T3", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 188, 197 ] ], "normalized": [] }, { "id": "PMID-10210645_T4", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 358, 367 ] ], "normalized": [] }, { "id": "PMID-10210645_T5", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 527, 536 ] ], "normalized": [] }, { "id": "PMID-10210645_T6", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 655, 664 ] ], "normalized": [] }, { "id": "PMID-10210645_T7", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 986, 995 ] ], "normalized": [] }, { "id": "PMID-10210645_T8", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1180, 1189 ] ], "normalized": [] }, { "id": "PMID-10210645_T9", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1291, 1300 ] ], "normalized": [] }, { "id": "PMID-10210645_T10", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1403, 1412 ] ], "normalized": [] }, { "id": "PMID-10210645_T11", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1500, 1509 ] ], "normalized": [] }, { "id": "PMID-10210645_T12", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1613, 1622 ] ], "normalized": [] }, { "id": "PMID-10210645_T13", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1731, 1740 ] ], "normalized": [] }, { "id": "PMID-10210645_T14", "type": "Protein", "text": [ "TNF-alpha" ], "offsets": [ [ 1905, 1914 ] ], "normalized": [] }, { "id": "PMID-10210645_T15", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 12, 21 ] ], "normalized": [] }, { "id": "PMID-10210645_T16", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 86, 94 ] ], "normalized": [] }, { "id": "PMID-10210645_T17", "type": "Entity", "text": [ "nuclear factor-kappa B" ], "offsets": [ [ 319, 341 ] ], "normalized": [] }, { "id": "PMID-10210645_T18", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 343, 352 ] ], "normalized": [] }, { "id": "PMID-10210645_T19", "type": "Entity", "text": [ "tyrosine" ], "offsets": [ [ 464, 472 ] ], "normalized": [] }, { "id": "PMID-10210645_T20", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 502, 511 ] ], "normalized": [] }, { "id": "PMID-10210645_T21", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 629, 638 ] ], "normalized": [] }, { "id": "PMID-10210645_T22", "type": "Entity", "text": [ "serine" ], "offsets": [ [ 824, 830 ] ], "normalized": [] }, { "id": "PMID-10210645_T23", "type": "Entity", "text": [ "/threonine" ], "offsets": [ [ 830, 840 ] ], "normalized": [] }, { "id": "PMID-10210645_T24", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1054, 1063 ] ], "normalized": [] }, { "id": "PMID-10210645_T25", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1154, 1163 ] ], "normalized": [] }, { "id": "PMID-10210645_T26", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 1164, 1167 ] ], "normalized": [] }, { "id": "PMID-10210645_T27", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1266, 1275 ] ], "normalized": [] }, { "id": "PMID-10210645_T28", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1378, 1387 ] ], "normalized": [] }, { "id": "PMID-10210645_T29", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 1388, 1391 ] ], "normalized": [] }, { "id": "PMID-10210645_T30", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1474, 1483 ] ], "normalized": [] }, { "id": "PMID-10210645_T31", "type": "Entity", "text": [ "DNA" ], "offsets": [ [ 1484, 1487 ] ], "normalized": [] }, { "id": "PMID-10210645_T32", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1588, 1597 ] ], "normalized": [] }, { "id": "PMID-10210645_T33", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1706, 1715 ] ], "normalized": [] }, { "id": "PMID-10210645_T34", "type": "Entity", "text": [ "NF-kappaB" ], "offsets": [ [ 1880, 1889 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-10210645_1", "entity_ids": [ "PMID-10210645_T2", "PMID-10210645_T3" ] } ]

[]

[ { "id": "PMID-1986254__text", "type": "abstract", "text": [ "Positive and negative regulation of immunoglobulin gene expression by a novel B-cell-specific enhancer element. \nA new B-cell-specific enhancer element has been identified 3' of E4 and the octamerlike motifs in the human immunoglobulin heavy-chain gene enhancer. Tandem copies of this 67-bp MnlI-AluI fragment, when fused to the chloramphenicol acetyltransferase gene driven by the conalbumin promoter, stimulated transcription in B cells but not in Jurkat T cells or HeLa cells. Footprinting analysis revealed that the identical sequence CCGAAACTGAAAAGG, designated E6, was protected by nuclear extracts from B cells, T cells, or HeLa cells. Gel mobility shift assays using a synthetic E6 motif detected a B-cell-specific complex in addition to a ubiquitous band found also in T cells and HeLa cells. In agreement with the results of gel retardation assays, tandem copies of the E6 motif stimulated transcription in ARH77 and Raji cells but not in Jurkat or HeLa cells. Furthermore, a mutant E6 motif lost both in vitro binding activity and in vivo enhancer activity. In striking contrast to the mouse Ig heavy-chain enhancer, in which the octamer motif acts as a B-cell-specific enhancer element, the human enhancer contains an octamerlike sequence with one base substitution which bound octamer-binding proteins with only very low affinity and showed no enhancer activity of its own. Interestingly, the MnlI-AluI fragment could suppress the basal-level activity of the conalbumin promoter in both Jurkat and HeLa cells. Moreover, simian virus 40 enhancer activity was blocked by the MnlI-AluI fragment in HeLa cells but not in B cells. Thus, the novel enhancer element identified in this study is probably a target site for both positive and negative factors.\n" ], "offsets": [ [ 0, 1763 ] ] } ]

[ { "id": "PMID-1986254_T1", "type": "Protein", "text": [ "chloramphenicol acetyltransferase" ], "offsets": [ [ 329, 362 ] ], "normalized": [] }, { "id": "PMID-1986254_T2", "type": "Protein", "text": [ "E6" ], "offsets": [ [ 567, 569 ] ], "normalized": [] }, { "id": "PMID-1986254_T3", "type": "Protein", "text": [ "E6" ], "offsets": [ [ 880, 882 ] ], "normalized": [] }, { "id": "PMID-1986254_T4", "type": "Protein", "text": [ "E6" ], "offsets": [ [ 993, 995 ] ], "normalized": [] }, { "id": "PMID-1986254_T5", "type": "Entity", "text": [ "immunoglobulin gene" ], "offsets": [ [ 36, 55 ] ], "normalized": [] }, { "id": "PMID-1986254_T6", "type": "Entity", "text": [ "B-cell-specific enhancer element" ], "offsets": [ [ 78, 110 ] ], "normalized": [] }, { "id": "PMID-1986254_T7", "type": "Entity", "text": [ "B-cell-specific enhancer element" ], "offsets": [ [ 119, 151 ] ], "normalized": [] }, { "id": "PMID-1986254_T8", "type": "Entity", "text": [ "E4" ], "offsets": [ [ 178, 180 ] ], "normalized": [] }, { "id": "PMID-1986254_T9", "type": "Entity", "text": [ "octamerlike motifs" ], "offsets": [ [ 189, 207 ] ], "normalized": [] }, { "id": "PMID-1986254_T10", "type": "Entity", "text": [ "human immunoglobulin heavy-chain gene enhancer" ], "offsets": [ [ 215, 261 ] ], "normalized": [] }, { "id": "PMID-1986254_T11", "type": "Entity", "text": [ "human immunoglobulin heavy-chain" ], "offsets": [ [ 215, 247 ] ], "normalized": [] }, { "id": "PMID-1986254_T12", "type": "Entity", "text": [ "Tandem copies" ], "offsets": [ [ 263, 276 ] ], "normalized": [] }, { "id": "PMID-1986254_T13", "type": "Entity", "text": [ "67-bp MnlI-AluI fragment" ], "offsets": [ [ 285, 309 ] ], "normalized": [] }, { "id": "PMID-1986254_T14", "type": "Entity", "text": [ "conalbumin promoter" ], "offsets": [ [ 382, 401 ] ], "normalized": [] }, { "id": "PMID-1986254_T15", "type": "Entity", "text": [ "CCGAAACTGAAAAGG" ], "offsets": [ [ 539, 554 ] ], "normalized": [] }, { "id": "PMID-1986254_T16", "type": "Entity", "text": [ "synthetic E6 motif" ], "offsets": [ [ 677, 695 ] ], "normalized": [] }, { "id": "PMID-1986254_T17", "type": "Entity", "text": [ "B-cell-specific complex" ], "offsets": [ [ 707, 730 ] ], "normalized": [] }, { "id": "PMID-1986254_T18", "type": "Entity", "text": [ "tandem copies" ], "offsets": [ [ 859, 872 ] ], "normalized": [] }, { "id": "PMID-1986254_T19", "type": "Entity", "text": [ "motif" ], "offsets": [ [ 883, 888 ] ], "normalized": [] }, { "id": "PMID-1986254_T20", "type": "Entity", "text": [ "motif" ], "offsets": [ [ 996, 1001 ] ], "normalized": [] }, { "id": "PMID-1986254_T21", "type": "Entity", "text": [ "mouse Ig heavy-chain enhancer" ], "offsets": [ [ 1097, 1126 ] ], "normalized": [] }, { "id": "PMID-1986254_T22", "type": "Entity", "text": [ "octamer motif" ], "offsets": [ [ 1141, 1154 ] ], "normalized": [] }, { "id": "PMID-1986254_T23", "type": "Entity", "text": [ "B-cell-specific enhancer element" ], "offsets": [ [ 1165, 1197 ] ], "normalized": [] }, { "id": "PMID-1986254_T24", "type": "Entity", "text": [ "human enhancer" ], "offsets": [ [ 1203, 1217 ] ], "normalized": [] }, { "id": "PMID-1986254_T25", "type": "Entity", "text": [ "octamerlike sequence" ], "offsets": [ [ 1230, 1250 ] ], "normalized": [] }, { "id": "PMID-1986254_T26", "type": "Entity", "text": [ "octamer-binding proteins" ], "offsets": [ [ 1290, 1314 ] ], "normalized": [] }, { "id": "PMID-1986254_T27", "type": "Entity", "text": [ "MnlI-AluI fragment" ], "offsets": [ [ 1406, 1424 ] ], "normalized": [] }, { "id": "PMID-1986254_T28", "type": "Entity", "text": [ "conalbumin promoter" ], "offsets": [ [ 1472, 1491 ] ], "normalized": [] }, { "id": "PMID-1986254_T29", "type": "Entity", "text": [ "MnlI-AluI fragment" ], "offsets": [ [ 1586, 1604 ] ], "normalized": [] }, { "id": "PMID-1986254_T30", "type": "Entity", "text": [ "novel enhancer element" ], "offsets": [ [ 1649, 1671 ] ], "normalized": [] } ]

[]

[]

[ { "id": "PMID-1986254_R1", "type": "Protein-Component", "arg1_id": "PMID-1986254_T4", "arg2_id": "PMID-1986254_T20", "normalized": [] } ]

[ { "id": "PMID-7983701__text", "type": "abstract", "text": [ "Inhibition of human immunodeficiency virus type 1 replication by a Tat-activated, transduced interferon gene: targeted expression to human immunodeficiency virus type 1-infected cells. \nWe have examined the feasibility of using interferon (IFN) gene transfer as a novel approach to anti-human immunodeficiency virus type 1 (HIV-1) therapy in this study. To limit expression of a transduced HIV-1 long terminal repeat (LTR)-IFNA2 (the new approved nomenclature for IFN genes is used throughout this article) hybrid gene to the HIV-1-infected cells, HIV-1 LTR was modified. Deletion of the NF-kappa B elements of the HIV-1 LTR significantly inhibited Tat-mediated transactivation in T-cell lines, as well as in a monocyte line, U937. Replacement of the NF-kappa B elements in the HIV-1 LTR by a DNA fragment derived from the 5'-flanking region of IFN-stimulated gene 15 (ISG15), containing the IFN-stimulated response element, partially restored Tat-mediated activation of LTR in T cells as well as in monocytes. Insertion of this chimeric promoter (ISG15 LTR) upstream of the human IFNA2 gene directed high levels of IFN synthesis in Tat-expressing cells, while this promoter was not responsive to tumor necrosis factor alpha-mediated activation. ISG15-LTR-IFN hybrid gene inserted into the retrovirus vector was transduced into Jurkat and U937 cells. Selected transfected clones produced low levels of IFN A (IFNA) constitutively, and their abilities to express interleukin-2 and interleukin-2 receptor upon stimulation with phytohemagglutinin and phorbol myristate acetate were retained. Enhancement of IFNA synthesis observed upon HIV-1 infection resulted in significant inhibition of HIV-1 replication for a period of at least 30 days. Virus isolated from IFNA-producing cells was able to replicate in the U937 cells but did not replicate efficiently in U937 cells transduced with the IFNA gene. These results suggest that targeting IFN synthesis to HIV-1-infected cells is an attainable goal and that autocrine IFN synthesis results in a long-lasting and permanent suppression of HIV-1 replication.\n" ], "offsets": [ [ 0, 2103 ] ] } ]

[ { "id": "PMID-7983701_T1", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 67, 70 ] ], "normalized": [] }, { "id": "PMID-7983701_T2", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 649, 652 ] ], "normalized": [] }, { "id": "PMID-7983701_T3", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 944, 947 ] ], "normalized": [] }, { "id": "PMID-7983701_T4", "type": "Protein", "text": [ "IFNA2" ], "offsets": [ [ 1081, 1086 ] ], "normalized": [] }, { "id": "PMID-7983701_T5", "type": "Protein", "text": [ "Tat" ], "offsets": [ [ 1133, 1136 ] ], "normalized": [] }, { "id": "PMID-7983701_T6", "type": "Protein", "text": [ "tumor necrosis factor alpha" ], "offsets": [ [ 1197, 1224 ] ], "normalized": [] }, { "id": "PMID-7983701_T7", "type": "Protein", "text": [ "IFN A" ], "offsets": [ [ 1402, 1407 ] ], "normalized": [] }, { "id": "PMID-7983701_T8", "type": "Protein", "text": [ "IFNA" ], "offsets": [ [ 1409, 1413 ] ], "normalized": [] }, { "id": "PMID-7983701_T9", "type": "Protein", "text": [ "interleukin-2" ], "offsets": [ [ 1462, 1475 ] ], "normalized": [] }, { "id": "PMID-7983701_T10", "type": "Protein", "text": [ "phytohemagglutinin" ], "offsets": [ [ 1525, 1543 ] ], "normalized": [] }, { "id": "PMID-7983701_T11", "type": "Protein", "text": [ "IFNA" ], "offsets": [ [ 1604, 1608 ] ], "normalized": [] }, { "id": "PMID-7983701_T12", "type": "Protein", "text": [ "IFNA" ], "offsets": [ [ 1759, 1763 ] ], "normalized": [] }, { "id": "PMID-7983701_T13", "type": "Protein", "text": [ "IFNA" ], "offsets": [ [ 1888, 1892 ] ], "normalized": [] }, { "id": "PMID-7983701_T14", "type": "Entity", "text": [ "Tat-activated, transduced interferon gene" ], "offsets": [ [ 67, 108 ] ], "normalized": [] }, { "id": "PMID-7983701_T15", "type": "Entity", "text": [ "interferon gene" ], "offsets": [ [ 93, 108 ] ], "normalized": [] }, { "id": "PMID-7983701_T16", "type": "Entity", "text": [ "HIV-1 long terminal repeat (LTR)-IFNA2" ], "offsets": [ [ 390, 428 ] ], "normalized": [] }, { "id": "PMID-7983701_T17", "type": "Entity", "text": [ "IFN genes" ], "offsets": [ [ 464, 473 ] ], "normalized": [] }, { "id": "PMID-7983701_T18", "type": "Entity", "text": [ "hybrid gene" ], "offsets": [ [ 507, 518 ] ], "normalized": [] }, { "id": "PMID-7983701_T19", "type": "Entity", "text": [ "HIV-1 LTR" ], "offsets": [ [ 548, 557 ] ], "normalized": [] }, { "id": "PMID-7983701_T20", "type": "Entity", "text": [ "NF-kappa B elements" ], "offsets": [ [ 588, 607 ] ], "normalized": [] }, { "id": "PMID-7983701_T21", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 588, 598 ] ], "normalized": [] }, { "id": "PMID-7983701_T22", "type": "Entity", "text": [ "HIV-1 LTR" ], "offsets": [ [ 615, 624 ] ], "normalized": [] }, { "id": "PMID-7983701_T23", "type": "Entity", "text": [ "NF-kappa B elements" ], "offsets": [ [ 751, 770 ] ], "normalized": [] }, { "id": "PMID-7983701_T24", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 751, 761 ] ], "normalized": [] }, { "id": "PMID-7983701_T25", "type": "Entity", "text": [ "HIV-1 LTR" ], "offsets": [ [ 778, 787 ] ], "normalized": [] }, { "id": "PMID-7983701_T26", "type": "Entity", "text": [ "5'-flanking region" ], "offsets": [ [ 823, 841 ] ], "normalized": [] }, { "id": "PMID-7983701_T27", "type": "Entity", "text": [ "IFN-stimulated gene 15" ], "offsets": [ [ 845, 867 ] ], "normalized": [] }, { "id": "PMID-7983701_T28", "type": "Entity", "text": [ "ISG15" ], "offsets": [ [ 869, 874 ] ], "normalized": [] }, { "id": "PMID-7983701_T29", "type": "Entity", "text": [ "IFN-stimulated response element" ], "offsets": [ [ 892, 923 ] ], "normalized": [] }, { "id": "PMID-7983701_T30", "type": "Entity", "text": [ "LTR" ], "offsets": [ [ 971, 974 ] ], "normalized": [] }, { "id": "PMID-7983701_T31", "type": "Entity", "text": [ "chimeric promoter" ], "offsets": [ [ 1029, 1046 ] ], "normalized": [] }, { "id": "PMID-7983701_T32", "type": "Entity", "text": [ "ISG15 LTR" ], "offsets": [ [ 1048, 1057 ] ], "normalized": [] }, { "id": "PMID-7983701_T33", "type": "Entity", "text": [ "ISG15-LTR-IFN hybrid gene" ], "offsets": [ [ 1246, 1271 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-7983701_1", "entity_ids": [ "PMID-7983701_T7", "PMID-7983701_T8" ] } ]

[]

[ { "id": "PMID-9209438__text", "type": "abstract", "text": [ "Of the GATA-binding proteins, only GATA-4 selectively regulates the human IL-5 gene promoter in IL-5 producing cells which express multiple GATA-binding proteins. \nInterleukin-5 (IL-5) is produced by T lymphocytes and known to support B cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region, within the human IL-5 gene promoter, that regulates IL-5 gene transcription. This cis-acting sequence contains the core binding motif, (A/T)GATA(A/G), for GATA-binding family proteins and thus suggests the involvement of these family members. In this report, we describe the cloning of human GATA-4 (hGATA-4) and show that hGATA-4 selectively interacts with the -70 GATA site within the IL-5 proximal promoter region. By promoter deletion and mutation analyses, we established this region as a positive regulatory element. Cotransfection experiments revealed that both hGATA-4 and PMA/A23187 stimulation are necessary for the IL-5 promoter activation. The requirement of another regulatory element called CLE0, which lies downstream of the -70 GATA site, was also demonstrated. ATL-16T cells express mRNA of three GATA-binding proteins, hGATA-2, hGATA-3 and hGATA-4, and each of them has a potential to bind to the consensus (A/T)GATA(G/ A) motif. However, using ATL-16T nuclear extract, we demonstrated that GATA-4 is the only GATA-binding protein that forms specific DNA-protein complex with the -70 GATA site. The electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity to the -70 GATA site among the three GATA-binding proteins. When the transactivation ability was compared among the three, GATA-4 showed the highest activity. These results demonstrate the selective role of GATA-4 in the transcriptional regulation of the IL-5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed.\n" ], "offsets": [ [ 0, 1997 ] ] } ]

[ { "id": "PMID-9209438_T1", "type": "Protein", "text": [ "GATA-4" ], "offsets": [ [ 35, 41 ] ], "normalized": [] }, { "id": "PMID-9209438_T2", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 74, 78 ] ], "normalized": [] }, { "id": "PMID-9209438_T3", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 96, 100 ] ], "normalized": [] }, { "id": "PMID-9209438_T4", "type": "Protein", "text": [ "Interleukin-5" ], "offsets": [ [ 164, 177 ] ], "normalized": [] }, { "id": "PMID-9209438_T5", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 179, 183 ] ], "normalized": [] }, { "id": "PMID-9209438_T6", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 341, 345 ] ], "normalized": [] }, { "id": "PMID-9209438_T7", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 398, 402 ] ], "normalized": [] }, { "id": "PMID-9209438_T8", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 433, 437 ] ], "normalized": [] }, { "id": "PMID-9209438_T9", "type": "Protein", "text": [ "human GATA-4" ], "offsets": [ [ 667, 679 ] ], "normalized": [] }, { "id": "PMID-9209438_T10", "type": "Protein", "text": [ "hGATA-4" ], "offsets": [ [ 681, 688 ] ], "normalized": [] }, { "id": "PMID-9209438_T11", "type": "Protein", "text": [ "hGATA-4" ], "offsets": [ [ 704, 711 ] ], "normalized": [] }, { "id": "PMID-9209438_T12", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 768, 772 ] ], "normalized": [] }, { "id": "PMID-9209438_T13", "type": "Protein", "text": [ "hGATA-4" ], "offsets": [ [ 950, 957 ] ], "normalized": [] }, { "id": "PMID-9209438_T14", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 1007, 1011 ] ], "normalized": [] }, { "id": "PMID-9209438_T15", "type": "Protein", "text": [ "hGATA-2" ], "offsets": [ [ 1218, 1225 ] ], "normalized": [] }, { "id": "PMID-9209438_T16", "type": "Protein", "text": [ "hGATA-3" ], "offsets": [ [ 1227, 1234 ] ], "normalized": [] }, { "id": "PMID-9209438_T17", "type": "Protein", "text": [ "hGATA-4" ], "offsets": [ [ 1239, 1246 ] ], "normalized": [] }, { "id": "PMID-9209438_T18", "type": "Protein", "text": [ "GATA-4" ], "offsets": [ [ 1390, 1396 ] ], "normalized": [] }, { "id": "PMID-9209438_T19", "type": "Protein", "text": [ "GATA-4" ], "offsets": [ [ 1607, 1613 ] ], "normalized": [] }, { "id": "PMID-9209438_T20", "type": "Protein", "text": [ "GATA-4" ], "offsets": [ [ 1770, 1776 ] ], "normalized": [] }, { "id": "PMID-9209438_T21", "type": "Protein", "text": [ "GATA-4" ], "offsets": [ [ 1854, 1860 ] ], "normalized": [] }, { "id": "PMID-9209438_T22", "type": "Protein", "text": [ "IL-5" ], "offsets": [ [ 1902, 1906 ] ], "normalized": [] }, { "id": "PMID-9209438_T23", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 84, 92 ] ], "normalized": [] }, { "id": "PMID-9209438_T24", "type": "Entity", "text": [ "region" ], "offsets": [ [ 373, 379 ] ], "normalized": [] }, { "id": "PMID-9209438_T25", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 408, 416 ] ], "normalized": [] }, { "id": "PMID-9209438_T26", "type": "Entity", "text": [ "cis-acting sequence" ], "offsets": [ [ 463, 482 ] ], "normalized": [] }, { "id": "PMID-9209438_T27", "type": "Entity", "text": [ "core binding motif" ], "offsets": [ [ 496, 514 ] ], "normalized": [] }, { "id": "PMID-9209438_T28", "type": "Entity", "text": [ "(A/T)GATA(A/G)" ], "offsets": [ [ 516, 530 ] ], "normalized": [] }, { "id": "PMID-9209438_T29", "type": "Entity", "text": [ "-70 GATA site" ], "offsets": [ [ 743, 756 ] ], "normalized": [] }, { "id": "PMID-9209438_T30", "type": "Entity", "text": [ "proximal promoter region" ], "offsets": [ [ 773, 797 ] ], "normalized": [] }, { "id": "PMID-9209438_T31", "type": "Entity", "text": [ "positive regulatory element" ], "offsets": [ [ 875, 902 ] ], "normalized": [] }, { "id": "PMID-9209438_T32", "type": "Entity", "text": [ "promoter" ], "offsets": [ [ 1012, 1020 ] ], "normalized": [] }, { "id": "PMID-9209438_T33", "type": "Entity", "text": [ "regulatory element" ], "offsets": [ [ 1060, 1078 ] ], "normalized": [] }, { "id": "PMID-9209438_T34", "type": "Entity", "text": [ "CLE0" ], "offsets": [ [ 1086, 1090 ] ], "normalized": [] }, { "id": "PMID-9209438_T35", "type": "Entity", "text": [ "-70 GATA site" ], "offsets": [ [ 1121, 1134 ] ], "normalized": [] }, { "id": "PMID-9209438_T36", "type": "Entity", "text": [ "consensus (A/T)GATA(G/ A) motif" ], "offsets": [ [ 1296, 1327 ] ], "normalized": [] }, { "id": "PMID-9209438_T37", "type": "Entity", "text": [ "(A/T)GATA(G/ A)" ], "offsets": [ [ 1306, 1321 ] ], "normalized": [] }, { "id": "PMID-9209438_T38", "type": "Entity", "text": [ "DNA-protein complex" ], "offsets": [ [ 1450, 1469 ] ], "normalized": [] }, { "id": "PMID-9209438_T39", "type": "Entity", "text": [ "-70 GATA site" ], "offsets": [ [ 1479, 1492 ] ], "normalized": [] }, { "id": "PMID-9209438_T40", "type": "Entity", "text": [ "-70 GATA site" ], "offsets": [ [ 1654, 1667 ] ], "normalized": [] } ]

[]

[ { "id": "PMID-9209438_1", "entity_ids": [ "PMID-9209438_T4", "PMID-9209438_T5" ] }, { "id": "PMID-9209438_2", "entity_ids": [ "PMID-9209438_T9", "PMID-9209438_T10" ] } ]

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[ { "id": "PMID-8709209__text", "type": "abstract", "text": [ "Various modes of basic helix-loop-helix protein-mediated regulation of murine leukemia virus transcription in lymphoid cell lines. \nThe transcriptionally regulatory regions of the lymphomagenic Akv and SL3-3 murine leukemia retroviruses (MLVs) contain two types of E-box consensus motifs, CAGATG. One type, EA/S, is located in the upstream promoter region, and the other, E(gre), is located in a tandem repeat with enhancer properties. We have examined the requirements of the individual E-boxes in MLV transcriptional regulation. In lymphoid cell lines only, the E(gre)-binding protein complexes included ALF1 or HEB and E2A basic helix-loop-helix proteins. Ectopic ALF1 and E2A proteins required intact E(gre) motifs for mediating transcriptional activation. ALF1 transactivated transcription of Akv MLV through the two E(gre) motifs equally, whereas E2A protein required the promoter-proximal E(gre) motif. In T- and B-cell lines, the E(gre) motifs were of major importance for Akv MLV transcriptional activity, while the EA/S motif had some effect. In contrast, neither E(gre) nor EA/S motifs contributed pronouncedly to Akv MLV transcription in NIH 3T3 cells lacking DNA-binding ALF1 or HEB and E2A proteins. The Id1 protein was found to repress ALF1 activity in vitro and in vivo. Moreover, ectopic Id1 repressed E(gre)-directed but not EA/S-directed MLV transcription in lymphoid cell lines. In conclusion, E(gre) motifs and interacting basic helix-loop-helix proteins are important determinants for MLV transcriptional activity in lymphocytic cell lines.\n" ], "offsets": [ [ 0, 1563 ] ] } ]

[ { "id": "PMID-8709209_T1", "type": "Protein", "text": [ "ALF1" ], "offsets": [ [ 606, 610 ] ], "normalized": [] }, { "id": "PMID-8709209_T2", "type": "Protein", "text": [ "HEB" ], "offsets": [ [ 614, 617 ] ], "normalized": [] }, { "id": "PMID-8709209_T3", "type": "Protein", "text": [ "ALF1" ], "offsets": [ [ 667, 671 ] ], "normalized": [] }, { "id": "PMID-8709209_T4", "type": "Protein", "text": [ "ALF1" ], "offsets": [ [ 761, 765 ] ], "normalized": [] }, { "id": "PMID-8709209_T5", "type": "Protein", "text": [ "ALF1" ], "offsets": [ [ 1184, 1188 ] ], "normalized": [] }, { "id": "PMID-8709209_T6", "type": "Protein", "text": [ "HEB" ], "offsets": [ [ 1192, 1195 ] ], "normalized": [] }, { "id": "PMID-8709209_T7", "type": "Protein", "text": [ "Id1" ], "offsets": [ [ 1218, 1221 ] ], "normalized": [] }, { "id": "PMID-8709209_T8", "type": "Protein", "text": [ "Id1" ], "offsets": [ [ 1305, 1308 ] ], "normalized": [] }, { "id": "PMID-8709209_T9", "type": "Entity", "text": [ "murine leukemia virus" ], "offsets": [ [ 71, 92 ] ], "normalized": [] }, { "id": "PMID-8709209_T10", "type": "Entity", "text": [ "transcriptionally regulatory regions" ], "offsets": [ [ 136, 172 ] ], "normalized": [] }, { "id": "PMID-8709209_T11", "type": "Entity", "text": [ "E-box consensus motifs" ], "offsets": [ [ 265, 287 ] ], "normalized": [] }, { "id": "PMID-8709209_T12", "type": "Entity", "text": [ "CAGATG" ], "offsets": [ [ 289, 295 ] ], "normalized": [] }, { "id": "PMID-8709209_T13", "type": "Entity", "text": [ "EA/S" ], "offsets": [ [ 307, 311 ] ], "normalized": [] }, { "id": "PMID-8709209_T14", "type": "Entity", "text": [ "upstream promoter region" ], "offsets": [ [ 331, 355 ] ], "normalized": [] }, { "id": "PMID-8709209_T15", "type": "Entity", "text": [ "E(gre)" ], "offsets": [ [ 372, 378 ] ], "normalized": [] }, { "id": "PMID-8709209_T16", "type": "Entity", "text": [ "tandem repeat" ], "offsets": [ [ 396, 409 ] ], "normalized": [] }, { "id": "PMID-8709209_T17", "type": "Entity", "text": [ "E-boxes" ], "offsets": [ [ 488, 495 ] ], "normalized": [] }, { "id": "PMID-8709209_T18", "type": "Entity", "text": [ "E(gre)" ], "offsets": [ [ 564, 570 ] ], "normalized": [] }, { "id": "PMID-8709209_T19", "type": "Entity", "text": [ "E(gre) motifs" ], "offsets": [ [ 705, 718 ] ], "normalized": [] }, { "id": "PMID-8709209_T20", "type": "Entity", "text": [ "E(gre) motifs" ], "offsets": [ [ 822, 835 ] ], "normalized": [] }, { "id": "PMID-8709209_T21", "type": "Entity", "text": [ "promoter-proximal E(gre) motif" ], "offsets": [ [ 878, 908 ] ], "normalized": [] }, { "id": "PMID-8709209_T22", "type": "Entity", "text": [ "E(gre) motifs" ], "offsets": [ [ 938, 951 ] ], "normalized": [] }, { "id": "PMID-8709209_T23", "type": "Entity", "text": [ "Akv MLV" ], "offsets": [ [ 981, 988 ] ], "normalized": [] }, { "id": "PMID-8709209_T24", "type": "Entity", "text": [ "EA/S motif" ], "offsets": [ [ 1025, 1035 ] ], "normalized": [] }, { "id": "PMID-8709209_T25", "type": "Entity", "text": [ "E(gre)" ], "offsets": [ [ 1074, 1080 ] ], "normalized": [] }, { "id": "PMID-8709209_T26", "type": "Entity", "text": [ "EA/S motifs" ], "offsets": [ [ 1085, 1096 ] ], "normalized": [] }, { "id": "PMID-8709209_T27", "type": "Entity", "text": [ "Akv MLV" ], "offsets": [ [ 1125, 1132 ] ], "normalized": [] }, { "id": "PMID-8709209_T28", "type": "Entity", "text": [ "ALF1" ], "offsets": [ [ 1251, 1255 ] ], "normalized": [] }, { "id": "PMID-8709209_T29", "type": "Entity", "text": [ "E(gre)" ], "offsets": [ [ 1319, 1325 ] ], "normalized": [] }, { "id": "PMID-8709209_T30", "type": "Entity", "text": [ "EA/S" ], "offsets": [ [ 1343, 1347 ] ], "normalized": [] }, { "id": "PMID-8709209_T31", "type": "Entity", "text": [ "E(gre)" ], "offsets": [ [ 1414, 1420 ] ], "normalized": [] }, { "id": "PMID-8709209_T32", "type": "Entity", "text": [ "MLV" ], "offsets": [ [ 1507, 1510 ] ], "normalized": [] } ]

[]

[]

[]

[ { "id": "PMID-9299589__text", "type": "abstract", "text": [ "Rel/NF-kappa B transcription factors and the control of apoptosis. \nThe process of apoptosis is used to eliminate unwanted cells from a wide variety of organisms. Various extracellular signals, often converging in common intracellular pathways, can induce apoptosis in a cell-type-specific fashion. Recent work from several laboratories has demonstrated that Rel/NF-kappa B transcription factors regulate apoptosis in many cell types. In most cells, Rel/NF-kappa B transcription factors appear to mediate survival signals that protect cells from apoptosis; however, under some circumstances, activation of these factors may also promote apoptosis.\n" ], "offsets": [ [ 0, 648 ] ] } ]

[ { "id": "PMID-9299589_T1", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 363, 373 ] ], "normalized": [] }, { "id": "PMID-9299589_T2", "type": "Entity", "text": [ "NF-kappa B" ], "offsets": [ [ 454, 464 ] ], "normalized": [] } ]

[]

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[]