tailieunhanh - Báo cáo khoa học: Oral Presentations Integration of Metabolism and Survival

The suppressors of cytokine signalling (SOCS) proteins inhibit cytokine signalling by direct interaction with Janus kinases (JAKs) or activated cytokine receptors. In addition to the N-ter-minal and SH2 domains that mediate these interactions, SOCS proteins contain a C-terminal SOCS box. Evidence suggests SOCS box-containing proteins act as part of an elongin-cullin-SOCS (ECS) E3 ubiquitin ligase complex, marking target pro-teins for degradation. | Abstracts Oral Presentations Integration of Metabolism and Survival OP-1 The ankyrin repeat and SOCS box-containing protein Asb-9 targets creatine kinase B for degradation M. A. Debrincat1 J. G. Zhang2 T. A. Willson3 B. T. Kile3 S. L. Masters2 L. M. Connolly4 R. J. Simpson4 H. M. Martin2 N. A. Nicola2 and D. J. Hilton3 ICancer and Haematology Molecular Medicine The Walter and Eliza Hall Institute of Medical Research Melbourne Australia 2Cancer and Haematology The Walter and Eliza Hall Institute of Medical Research Melbourne Australia 3Molecular Medicine The Walter and Eliza Hall Institute of Medical Research Melbourne Australia4The Joint Proteomics Laboratory of the Walter and Eliza Hall Institute of Medical Research and Ludwig Institute for Cancer Research Melbourne Australia. E-mail debrincat@ The suppressors of cytokine signalling SOCS proteins inhibit cytokine signalling by direct interaction with Janus kinases JAKs or activated cytokine receptors. In addition to the N-ter-minal and SH2 domains that mediate these interactions SOCS proteins contain a C-terminal SOCS box. Evidence suggests SOCS box-containing proteins act as part of an elongin-cullin-SOCS ECS E3 ubiquitin ligase complex marking target proteins for degradation. The specificity of the complex is determined by the protein interaction motif located upstream from the SOCS box. A number of other protein families that possess a SOCS box have been identified the largest of which are the ank-yrin repeat and SOCS box-containing Asbs. While it is known that the SOCS proteins are involved in the negative regulation of cytokine signalling the biological and biochemical functions of the Asbs are undefined. To understand the functional role of Asb proteins a proteomic approach was implemented and creatine kinase B CKB was identified as a specific binding partner of Asb-9. Transfection of increasing concentrations of a tagged Asb-9 construct into 293T cells increased the polyubiquitination of CKB and

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