title: Vinexin beta interacts with the non-phosphorylated AF-1 domain of retinoid receptor gamma (RARgamma) and represses RARgamma-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 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.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, Unité Mixte de Recherche 7104, 67404 Illkirch Cedex, France.
authors.forename: Gaétan
authors.initials: G
authors.lastname: Bour
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Plassat
authors.forename: Annie
authors.initials: A
authors.lastname: Bauer
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lalevée
authors.forename: Cécile
authors.initials: C
authors.lastname: Rochette-Egly
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D001616:beta-Galactosidase / Q000378:metabolism; D018909:src Homology Domains; D000097768:Retinoic Acid Receptor gamma
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015500:Chloramphenicol O-Acetyltransferase; D018076:DNA, Complementary; D005982:Glutathione Transferase; D009124:Muscle Proteins; D012313:RNA; D034741:RNA, Small Interfering; D018168:Receptors, Retinoic Acid; D014212:Tretinoin; D001616:beta-Galactosidase; D000097768:Retinoic Acid Receptor gamma; C486523:SORBS3 protein, human; C117452:Sorbs3 protein, mouse