Vinexin β Interacts with the Non-phosphorylated AF-1 Domain of Retinoid Receptor γ (RARγ) and Represses RARγ-mediated Transcription

Abstract 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.