Vinexin beta interacts with the non-phosphorylated AF-1 domain of retinoid receptor gamma (RARgamma) and represses RARgamma-mediated transcription.

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Bour, Gaétan | Plassat, Jean-Luc | Bauer, Annie | Lalevée, Sébastien | Rochette-Egly, Cécile

Edité par CCSD ; American Society for Biochemistry and Molecular Biology -

International audience. 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 beta as a new cofactor that interacts with the N-terminal A/B domain of the RARgamma isotype. Vinexin beta is a multiple SH3 motif-containing protein associated with the cytoskeleton and also present in the nucleus. We demonstrate that vinexin beta colocalizes with RARgamma in the nucleus and interacts with the non-phosphorylated form of the AF-1 domain of RARgamma. We also show that this interaction is prevented upon phosphorylation of the AF-1 domain. Using F9 cells stably overexpressing vinexin beta or vinexin knockdown by RNA interference, we demonstrate that vinexin beta is an inhibitor of RARgamma-mediated transcription. We propose a model in which phosphorylation of the AF-1 domain controls RARgamma-mediated transcription through triggering the dissociation of vinexin beta.

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