Regulation of glucocorticoid receptor activity by 14-3-3-dependent intracellular relocalization of the corepressor RIP140

Citation
J. Zilliacus et al., Regulation of glucocorticoid receptor activity by 14-3-3-dependent intracellular relocalization of the corepressor RIP140, MOL ENDOCR, 15(4), 2001, pp. 501-511
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
MOLECULAR ENDOCRINOLOGY
ISSN journal
0888-8809 → ACNP
Volume
15
Issue
4
Year of publication
2001
Pages
501 - 511
Database
ISI
SICI code
0888-8809(200104)15:4<501:ROGRAB>2.0.ZU;2-R
Abstract
Proteins belonging to the 14-3-3 family interact with various regulatory pr oteins involved in cellular signaling, cell cycle regulation, or apoptosis, 14-3-3 proteins have been suggested to act by regulating the cytoplasmic/n uclear localization of their target proteins or by acting as molecular scaf folds or chaperones. We have previously shown that overexpression of 14-3-3 enhances the transcriptional activity of the glucocorticoid receptor (GR), which is a member of the nuclear receptor family. In this study, we show t hat 14-3-3 interacts with the nuclear receptor corepressor RIP140, In trans fection assays, RIP140 antagonizes 14-3-3-enhanced GR transactivation, Usin g colocalization studies we demonstrate that 14-3-3 can export RIP140 out o f the nucleus and, interestingly, can also change its intranuclear localiza tion. Moreover, we also observed that 14-3-3 can bind various other nuclear receptors and cofactors, In summary, our findings suggest that 14-3-3-medi ated intracellular relocalization of the GR corepressor RIP140 might be a n ovel mechanism to enhance glucocorticoid responsiveness of target genes. Th ey furthermore indicate a more general role for 14-3-3 protein by influenci ng the nuclear availability of nuclear receptor-associated cofactors.