The role of calpains in ligand-induced degradation of the glucocorticoid receptor

Yoon Suk Kim, Jeonghan Kim, Yoonseo Kim, Young Han Lee, Jae-Hong Kim, Seung Jae Lee, Soon Young Shin, Je Sang Ko

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The glucocorticoid receptor (GR) is a ligand-activated transcription factor that mediates the effects of glucocorticoids in diverse cellular processes, including homeostasis, stress response, and inflammation. Glucocorticoids induce down-regulation of GR at both the mRNA and protein levels, causing reduced hormone responsiveness in response to long-term treatment with glucocorticoid. However, the mechanism involved in this process is still obscure. In this study, we examined whether calpain, a calcium-activated cysteine protease, is involved in ligand-stimulated degradation of GR. In COS-7 cells expressing the human GR, treatment with a calpain inhibitor abolished glucocorticoid-induced down-regulation of GR in a dose dependent manner. The protein level of endogenous GR was also elevated by inhibition of the calpain activity in HeLa cells treated with glucocorticoid. Furthermore, glucocorticoid-induced transcriptional activation of GR was enhanced in cells treated with a calpain inhibitor. These results indicate that calpain is involved in ligand-dependent degradation of GR, thus causing reduced hormone responsiveness.

Original languageEnglish
Pages (from-to)373-377
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume374
Issue number2
DOIs
Publication statusPublished - 2008 Sep 19

Keywords

  • Calpain
  • Dexamethasone
  • Glucocorticoid receptor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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