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, Je Sang Ko

Research output: Contribution to journalArticle

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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 1

Fingerprint

Glucocorticoid Receptors
Transcriptional Activation
Glucocorticoids
Ligands
Signal Transduction
14-3-3 Proteins
Cytoplasmic and Nuclear Receptors
Ubiquitin
HeLa Cells
Cytosol

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Role of 14-3-3η as a positive regulator of the glucocorticoid receptor transcriptional activation. / Kim, Yoon Suk; Jang, Sung Wuk; Sung, Ho Joong; Lee, Hye Jin; Kim, In Sik; Na, Doe Sun; Ko, Je Sang.

In: Endocrinology, Vol. 146, No. 7, 01.07.2005, p. 3133-3140.

Research output: Contribution to journalArticle

Kim, Yoon Suk ; Jang, Sung Wuk ; Sung, Ho Joong ; Lee, Hye Jin ; Kim, In Sik ; Na, Doe Sun ; Ko, Je Sang. / Role of 14-3-3η as a positive regulator of the glucocorticoid receptor transcriptional activation. In: Endocrinology. 2005 ; Vol. 146, No. 7. pp. 3133-3140.
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