Role of 14-3-3η as a positive regulator of the glucocorticoid receptor transcriptional activation

Yoon Suk Kim, Sung Wuk Jang, Ho Joong Sung, Hye Jin Lee, In Sik Kim, Doe Sun Na, Jesang Ko

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The glucocorticoid receptor (GR), a member of the nuclear receptor superfamily, mediates the effects of glucocorticoids. It is known that 14-3-3 family proteins interact with GR and regulate its transcriptional activity. They also bind to several molecules and influence many cellular events by altering their subcellular localization and/or acting as a chaperone. Recently, it has been proposed that ligand-activated degradation of GR occurs via the ubiquitin-proteasomal degradation pathway and that inhibition of proteasomal activity induces up-regulation of GR and enhances the transcriptional activity of GR. To examine the function of 14-3-3η in the glucocorticoid-dependent signal pathway, we studied the regulatory role of 14-3-3η in ligand-induced GR transcriptional activation. 14-3-3η Enhanced the transcriptional activity of GR, and the levels of GR were higher in cells transfected with the 14-3-3η expression vector in response to glucocorticoid. The GR level increased in both cytosol and nucleus, and endogenous GR was also elevated by 14-3-3η in HeLa cells. 14-3-3η Inhibited ligand-induced down-regulation of GR. Proteasomal inhibition did not induce any synergistic effect on the 14-3-3η-induced increase in GR in response to glucocorticoid, and inhibition of translation did not block elevation of GR by 14-3-3η, indicating that 14-3-3η induces stabilization of GR. These results suggest that 14-3-3η functions as a positive regulator in the glucocorticoid signal pathway by blocking the degradation of GR and inducing an elevation of GR, thus enhancing the transcriptional activity of GR.

Original languageEnglish
Pages (from-to)3133-3140
Number of pages8
JournalEndocrinology
Volume146
Issue number7
DOIs
Publication statusPublished - 2005 Jul

ASJC Scopus subject areas

  • Endocrinology

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