Vinexin β Interacts with the Non-phosphorylated AF-1 Domain of Retinoid Receptor γ (RARγ) and Represses RARγ-mediated Transcription
| Autor: | Sébastien Lalevée, Jean-Luc Plassat, Cécile Rochette-Egly, Annie Bauer, Gaétan Bour |
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| Rok vydání: | 2005 |
| Předmět: |
0303 health sciences
Gene knockdown 030302 biochemistry & molecular biology Retinoic acid Retinoid receptor Cell Biology Biology Biochemistry Molecular biology Cell biology 03 medical and health sciences chemistry.chemical_compound chemistry Transcription (biology) RNA interference Phosphorylation Receptor Molecular Biology Transcription factor 030304 developmental biology |
| Zdroj: | Journal of Biological Chemistry. 280:17027-17037 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m501344200 |
| Popis: | Nuclear retinoic acid receptors (RARs) are ligand-dependent transcription factors that regulate the expression of retinoic acid target genes. Although the importance of RAR phosphorylation in their N-terminal domain is clearly established, the underlying mechanism for the phosphorylation-dependent transcriptional activity of the receptors had not been elucidated yet. Here, using a yeast two-hybrid system, we report the isolation of vinexin β as a new cofactor that interacts with the N-terminal A/B domain of the RARγ isotype. Vinexin β is a multiple SH3 motif-containing protein associated with the cytoskeleton and also present in the nucleus. We demonstrate that vinexin β colocalizes with RARγ in the nucleus and interacts with the non-phosphorylated form of the AF-1 domain of RARγ. We also show that this interaction is prevented upon phosphorylation of the AF-1 domain. Using F9 cells stably overexpressing vinexin β or vinexin knockdown by RNA interference, we demonstrate that vinexin β is an inhibitor of RARγ-mediated transcription. We propose a model in which phosphorylation of the AF-1 domain controls RARγ-mediated transcription through triggering the dissociation of vinexin β. |
| Databáze: | OpenAIRE |
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