human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: EBV latent antigen EBNA3C is indispensible for in vitro B-cell immortalization resulting in continuously proliferating lymphoblastoid cell lines ( LCLs ) . EBNA3C was previously shown to target pRb for ubiquitin-proteasome mediated degradation , which facilitates G1 to S transition controlled by the major transcriptional activator E2F1 . E2F1 also plays a pivotal role in regulating DNA damage induced apoptosis through both p53-dependent and -independent pathways . In this study , we demonstrate that in response to DNA damage LCLs knocked down for EBNA3C undergo a drastic induction of apoptosis , as a possible consequence of both p53- and E2F1-mediated activities . Importantly , EBNA3C was previously shown to suppress p53-induced apoptosis . Now , we also show that EBNA3C efficiently blocks E2F1-mediated apoptosis , as well as its anti-proliferative effects in a p53-independent manner , in response to DNA damage . The N- and C-terminal domains of EBNA3C form a stable pRb independent complex with the N-terminal DNA-binding region of E2F1 responsible for inducing apoptosis . Mechanistically , we show that EBNA3C represses E2F1 transcriptional activity via blocking its DNA-binding activity at the responsive promoters of p73 and Apaf-1 apoptosis induced genes , and also facilitates E2F1 degradation in an ubiquitin-proteasome dependent fashion . Moreover , in response to DNA damage , E2F1 knockdown LCLs exhibited a significant reduction in apoptosis with higher cell-viability . In the presence of normal mitogenic stimuli the growth rate of LCLs knockdown for E2F1 was markedly impaired ; indicating that E2F1 plays a dual role in EBV positive cells and that active engagement of the EBNA3C-E2F1 complex is crucial for inhibition of DNA damage induced E2F1-mediated apoptosis . This study offers novel insights into our current understanding of EBV biology and enhances the potential for development of effective therapies against EBV associated B-cell lymphomas .
    OUTPUT:

agent
genomic instability and mutation;resisting cell death
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: EBV latent antigen EBNA3C is indispensible for in vitro B-cell immortalization resulting in continuously proliferating lymphoblastoid cell lines ( LCLs ) . EBNA3C was previously shown to target pRb for ubiquitin-proteasome mediated degradation , which facilitates G1 to S transition controlled by the major transcriptional activator E2F1 . E2F1 also plays a pivotal role in regulating DNA damage induced apoptosis through both p53-dependent and -independent pathways . In this study , we demonstrate that in response to DNA damage LCLs knocked down for EBNA3C undergo a drastic induction of apoptosis , as a possible consequence of both p53- and E2F1-mediated activities . Importantly , EBNA3C was previously shown to suppress p53-induced apoptosis . Now , we also show that EBNA3C efficiently blocks E2F1-mediated apoptosis , as well as its anti-proliferative effects in a p53-independent manner , in response to DNA damage . The N- and C-terminal domains of EBNA3C form a stable pRb independent complex with the N-terminal DNA-binding region of E2F1 responsible for inducing apoptosis . Mechanistically , we show that EBNA3C represses E2F1 transcriptional activity via blocking its DNA-binding activity at the responsive promoters of p73 and Apaf-1 apoptosis induced genes , and also facilitates E2F1 degradation in an ubiquitin-proteasome dependent fashion . Moreover , in response to DNA damage , E2F1 knockdown LCLs exhibited a significant reduction in apoptosis with higher cell-viability . In the presence of normal mitogenic stimuli the growth rate of LCLs knockdown for E2F1 was markedly impaired ; indicating that E2F1 plays a dual role in EBV positive cells and that active engagement of the EBNA3C-E2F1 complex is crucial for inhibition of DNA damage induced E2F1-mediated apoptosis . This study offers novel insights into our current understanding of EBV biology and enhances the potential for development of effective therapies against EBV associated B-cell lymphomas .
    OUTPUT:
