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

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.
Mesh Terms:
14-3-3 Proteins, Adaptor Proteins, Signal Transducing, Animals, COS Cells, Cell Nucleus, Cytoplasm, Nuclear Proteins, Phosphorylation, Receptors, Androgen, Receptors, Cytoplasmic and Nuclear, Receptors, Estrogen, Receptors, Glucocorticoid, Receptors, Retinoic Acid, Repressor Proteins, Retinoid X Receptors, Subcellular Fractions, Transcription Factors, Transcriptional Activation, Tyrosine 3-Monooxygenase
Mol. Endocrinol.
Date: Apr. 01, 2001
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