Vinexinß, an atypical "sensor" of retinoic acid receptor gamma signaling: union and sequestration, separation, and phosphorylation

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Sébastien LalevéeC Rochette-Egly

Abstract

The transcriptional activity of nuclear retinoic acid receptors (RARs) relies on the association/dissociation of coregulators at the ligand-binding domain. However, we determined that the N-terminal domain (NTD) also plays a role through its phosphorylation, and we isolated vinexinβ, a cytoskeleton protein with three SH3 domains, as a new partner of the RARγ NTD. Here we deciphered the mechanism of the interaction and its role in RARγ-mediated transcription. By combining molecular and biophysical (surface plasmon resonance, NMR, and fluorescence resonance energy transfer) approaches, we demonstrated that the third SH3 domain of vinexinβ interacts with a proline-rich domain (PRD) located in RARγ NTD and that phosphorylation at a serine located in the PRD abrogates the interaction. The affinity of the interaction was also evaluated. In vivo, vinexinβ represses RARγ-mediated transcription and we dissected the underlying mechanism in chromatin immunoprecipitation experiments performed with F9 cells expressing RARγ wild type or mutated at the phosphorylation site. In the absence of retinoic acid (RA), vinexinβ does not occupy RARγ target gene promoters and sequesters nonphosphorylated RARγ out of promoters. In response to RA, RARγ b...Continue Reading

References

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Citations

Feb 27, 2013·Journal of Lipid Research·Ziad Al TanouryCécile Rochette-Egly
Oct 16, 2015·Canadian Journal of Physiology and Pharmacology·Madina IskakovaCécile Rochette-Egly
Apr 22, 2015·Nucleic Acids Research·Amandine ChatagnonGérard Benoit
Dec 30, 2014·Molecular Aspects of Medicine·Alessandra di MasiClara Nervi
Jul 26, 2011·Molecular and Cellular Endocrinology·Jun Yang, Peter J Fuller
Oct 13, 2011·Molecular and Cellular Endocrinology·Harri Itkonen, Ian G Mills
Jan 27, 2017·PloS One·Yassmine ChebaroAnnick Dejaegere
Jan 16, 2014·Molecular Endocrinology·Eric SamarutVincent Laudet
Oct 26, 2010·Biochimica Et Biophysica Acta·Vanessa Duong, Cécile Rochette-Egly
Apr 21, 2011·Molecular and Cellular Endocrinology·Eric Samarut, Cécile Rochette-Egly

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