Unbiased identification of substrates for the Epac1-inducible E3 ubiquitin ligase component SOCS-3

Williams, J. J.L. and Palmer, T. M. (2012) Unbiased identification of substrates for the Epac1-inducible E3 ubiquitin ligase component SOCS-3. Biochemical Society Transactions, 40(1), pp. 215-218. (doi: 10.1042/BST20110629) (PMID:22260693)

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Publisher's URL: http://dx.doi.org/10.1042/BST20110629

Abstract

The anti-inflammatory effects of the prototypical second messenger cAMP have been extensively documented in multiple cell types. One mechanism by which these effects are achieved is via Epac1 (exchange protein directly activated by cAMP 1)-dependent induction of SOCS-3 (suppressor of cytokine signalling 3), which binds and inhibits specific class I cytokine receptors. One important aspect of SOCS-3 functionality is its role as the specificity determinant within an E3 ubiquitin ligase complex which targets cellular substrates for polyubiquitylation and proteasomal degradation. In the present review, we describe key inhibitory processes that serve to reduce cytokine receptor signalling, focusing primarily on SOCS protein function and regulation. We also outline a strategy we have developed to identify novel ubiquitylated substrates for the Epac1-inducible SOCS-3 E3 ubiquitin ligase complex following purification of the ubiquitinome. It is anticipated that identifying substrates for the Epac1-regulated SOCS-3 E3 ubiquitin ligase, and assessment of their functional significance, may pinpoint new sites for therapeutic intervention that would achieve therapeutic efficacy of cAMP-elevating drugs while minimizing the adverse effects usually associated with these agents.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Palmer, Dr Timothy and Williams, Dr Jamie
Authors: Williams, J. J.L., and Palmer, T. M.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Biochemical Society Transactions
Publisher:Portland Press Ltd.
ISSN:0300-5127
ISSN (Online):1470-8752
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
498581EPAC1 and ERK-dependent activation of C/EBP transcription factors: a new cyclic AMP-activated anti-inflammatory gene expression module in vascular endothelial cellsTimothy PalmerBritish Heart Foundation (BHF)PG/08/125/26415Institute of Cardiovascular and Medical Sciences
500151Doctoral Training Grant 2009-15Timothy PalmerBiotechnology and Biological Sciences Research Council (BBSRC)BB/F016735/1RI CARDIOVASCULAR & MEDICAL SCIENCES
500152Doctoral Training Grant 2009-15Timothy PalmerBiotechnology and Biological Sciences Research Council (BBSRC)BB/F016735/1RI CARDIOVASCULAR & MEDICAL SCIENCES