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

Johanna Zilliacus, Elin Holter, Hideki Wakui, Hiroshi Tazawa, Eckardt Treuter, Jan Åke Gustafsson

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Proteins belonging to the 14-3-3 family interact with various regulatory proteins involved in cellular signaling, cell cycle regulation, or apoptosis. 14-3-3 proteins have been suggested to act by regulating the cytoplasmic/nuclear localization of their target proteins or by acting as molecular scaffolds 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 that 14-3-3 interacts with the nuclear receptor corepressor RIP140. In transfection assays, RIP140 antagonizes 14-3-3-enhanced GR transactivation. Using colocalization studies we demonstrate that 14-3-3 can export RIP140 out of the nucleus and, interestingly, can also change its intranuclear localization. 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-mediated intracellular relocalization of the GR corepressor RIP140 might be a novel mechanism to enhance glucocorticoid responsiveness of target genes. They furthermore indicate a more general role for 14-3-3 protein by influencing the nuclear availability of nuclear receptor-associated cofactors.

Original languageEnglish (US)
Pages (from-to)501-511
Number of pages11
JournalMolecular Endocrinology
Volume15
Issue number4
DOIs
StatePublished - May 1 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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