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, Jesang Ko

    Research output: Contribution to journalArticlepeer-review

    4 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 Sept 19

    Bibliographical note

    Funding Information:
    This work was supported by the Korea Science and Engineering Foundation (KOSEF) Grant funded by the Korea government (MOST) (R01-2007-000-10778-0) and a Grant from the Diseases Network Research Program (M10751050002-07N5105-00210), Ministry of Science and Technology, South Korea.

    Keywords

    • Calpain
    • Dexamethasone
    • Glucocorticoid receptor

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

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