Ankyrin repeat and suppressors of cytokine signaling box protein asb-9 targets creatine kinase B for degradation.
The suppressors of cytokine signaling (SOCS) proteins inhibit cytokine action by direct interaction with Janus kinases or activated cytokine receptors. In addition to the N-terminal and Src homology 2 domains that mediate these interactions, SOCS proteins contain a C-terminal SOCS box. DNA data base searches have identified a number of other protein families that possess a SOCS box, of which the ankyrin repeat and SOCS box-containing (Asb) proteins constitute the largest. Although it is known that the SOCS proteins are involved in the negative regulation of cytokine signaling, the biological and biochemical functions of the Asbs are largely undefined. Using a proteomics approach, we demonstrate that creatine kinase B (CKB) interacts with Asb-9 in a specific, SOCS box-independent manner. This interaction increases the polyubiquitylation of CKB and decreases total CKB levels within the cell. The targeting of CKB for degradation by Asb-9 was primarily SOCS box-dependent and suggests that Asb-9 acts as a specific ubiquitin ligase regulating levels of this evolutionarily conserved enzyme.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-N GENE-N GENE-Y GENE-Y
N C creatine creatine Asb-9 ubiquitin ligase Janus kinases cytokine receptors Src homology 2 domains SOCS SOCS box SOCS box ankyrin SOCS box Asb suppressors of cytokine signaling (SOCS) proteins SOCS cytokine cytokine Asbs creatine kinase B CKB Asb-9 SOCS box CKB CKB CKB Asb-9 SOCS box Ankyrin cytokine signaling box protein asb-9 creatine kinase B