title: Role of 14-3-3 eta as a positive regulator of the glucocorticoid receptor transcriptional activation.
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 14-3-3eta 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.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, 5-1 Anam-dong, Sungbuk-gu, Seoul 136-701, South Korea.
authors.forename: Yoon Suk
authors.initials: YS
authors.lastname: Kim
authors.forename: Sung-Wuk
authors.initials: SW
authors.lastname: Jang
authors.forename: Ho Joong
authors.initials: HJ
authors.lastname: Sung
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: In Sik
authors.initials: IS
authors.lastname: Kim
authors.forename: Doe Sun
authors.initials: DS
authors.lastname: Na
authors.forename: Jesang
authors.initials: J
authors.lastname: Ko
mesh_terms: D048948:14-3-3 Proteins / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004355:Drug Stability; D005938:Glucocorticoids / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*
chemical_list: D048948:14-3-3 Proteins; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone