SGK-1 (serum- and glucocorticoid-regulated kinase-1) is a stress-induced serine/threonine kinase that is phosphorylated and activated downstream of PI3K (phosphoinositide 3-kinase). SGK-1 plays a critical role in insulin signalling, cation transport and cell survival. SGK-1 mRNA expression is transiently induced following cellular stress, and SGK-1 protein levels are tightly regulated by rapid proteasomal degradation. In the present study we report that SGK-1 forms a complex with the stress-associated E3 ligase CHIP [C-terminus of Hsc (heat-shock cognate protein) 70-interacting protein]; CHIP is required for both the ubiquitin modification and rapid proteasomal degradation of SGK-1. We also show that CHIP co-localizes with SGK-1 at or near the endoplasmic reticulum. CHIP-mediated regulation of SGK-1 steady-state levels alters SGK-1 kinase activity. These data suggest a model that integrates CHIP function with regulation of the PI3K/SGK-1 pathway in the stress response.
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December 2006
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Research Article|
November 14 2006
Ubiquitin–proteasome degradation of serum- and glucocorticoid-regulated kinase-1 (SGK-1) is mediated by the chaperone-dependent E3 ligase CHIP
Larissa Belova;
Larissa Belova
*Department of Medicine and Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, U.S.A.
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Sanjay Sharma;
Sanjay Sharma
*Department of Medicine and Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, U.S.A.
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Deanna R. Brickley;
Deanna R. Brickley
*Department of Medicine and Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, U.S.A.
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Jeremy R. Nicolarsen;
Jeremy R. Nicolarsen
*Department of Medicine and Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, U.S.A.
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Cam Patterson;
Cam Patterson
†Carolina Cardiovascular Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, U.S.A.
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Suzanne D. Conzen
Suzanne D. Conzen
1
*Department of Medicine and Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, U.S.A.
1To whom correspondence should be addressed (sconzen@medicine.bsd.uchicago.edu).
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Publisher: Portland Press Ltd
Received:
June 15 2006
Revision Received:
July 24 2006
Accepted:
August 07 2006
Accepted Manuscript online:
August 08 2006
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 400 (2): 235–244.
Article history
Received:
June 15 2006
Revision Received:
July 24 2006
Accepted:
August 07 2006
Accepted Manuscript online:
August 08 2006
Citation
Larissa Belova, Sanjay Sharma, Deanna R. Brickley, Jeremy R. Nicolarsen, Cam Patterson, Suzanne D. Conzen; Ubiquitin–proteasome degradation of serum- and glucocorticoid-regulated kinase-1 (SGK-1) is mediated by the chaperone-dependent E3 ligase CHIP. Biochem J 1 December 2006; 400 (2): 235–244. doi: https://doi.org/10.1042/BJ20060905
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