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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 
 ENDOCRINOLOGY, Vol.146(7) : 3133-3140, 2005 
Journal Title
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14-3-3 Proteins/physiology* ; Animals ; COS Cells ; Cercopithecus aethiops ; Dexamethasone/pharmacology ; Down-Regulation/drug effects ; Down-Regulation/physiology ; Drug Stability ; Glucocorticoids/pharmacology ; HeLa Cells ; Humans ; Receptors, Glucocorticoid/chemistry ; Receptors, Glucocorticoid/genetics* ; Receptors, Glucocorticoid/metabolism ; Transcriptional Activation/drug effects ; Transcriptional Activation/physiology*
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 14-3-3eta in the glucocorticoid-dependent signal pathway, we studied the regulatory role of 14-3-3eta in ligand-induced GR transcriptional activation. 14-3-3eta Enhanced the transcriptional activity of GR, and the levels of GR were higher in cells transfected with the 14-3-3eta expression vector in response to glucocorticoid. The GR level increased in both cytosol and nucleus, and endogenous GR was also elevated by 14-3-3eta in HeLa cells. 14-3-3eta Inhibited ligand-induced down-regulation of GR. Proteasomal inhibition did not induce any synergistic effect on the 14-3-3eta-induced increase in GR in response to glucocorticoid, and inhibition of translation did not block elevation of GR by 14-3-3eta, indicating that 14-3-3eta induces stabilization of GR. These results suggest that 14-3-3eta 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.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Koh, Hyoung Jun(고형준) ORCID logo https://orcid.org/0000-0002-5932-8516
Kwon, Oh Woong(권오웅)
Lee, Sung Chul(이성철) ORCID logo https://orcid.org/0000-0001-9438-2385
Lee, Joon Haeng(이준행)
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