Ubiquitin-proteasome degradation of serum- and glucocorticoid-regulated kinase-1 (SGK-1) is mediated by the chaperone-dependent E3 ligase CHIP

Larissa Belova, Sanjay Sharma, Deanna R. Brickley, Jeremy R. Nicolarsen, Cam Patterson, Suzanne D. Conzen

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)235-244
Number of pages10
JournalBiochemical Journal
Volume400
Issue number2
DOIs
StatePublished - Dec 1 2006

Keywords

  • C-terminus of Hsc70 interacting protein (CHIP) E3 ligase
  • Cell survival
  • Phosphoinositide 3-kinase (PI3K)
  • Serum and glucocorticoid-regulated kinase-1 (SGK-1)
  • Stress response
  • Ubiquitination

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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