Ankyrin repeat and suppressors of cytokine signaling box protein asb-9 targets creatine kinase B for degradation.
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Debrincat MA, Zhang JG, Willson TA, Silke J, Connolly LM, Simpson RJ, Alexander WS, Nicola NA, Kile BT, Hilton DJ
Ankyrin repeat and suppressors of cytokine signaling box protein asb-9 targets creatine kinase B for degradation.
J Biol Chem. 2007 Feb 16;282(7):4728-37. Epub 2006 Dec 5.
- PubMed ID
- 17148442 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Creatine Creatine kinase B-type Protein Humans YesLigandDetails