Fiche publication
Date publication
juillet 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROCHETTE-EGLY Cécile
Tous les auteurs :
Piskunov A, Rochette-Egly C
Lien Pubmed
Résumé
Retinoic acid (RA) regulates several gene programs by nuclear RA receptors (RARs) that are ligand-dependent transcriptional transregulators. The basic mechanism for switching on transcription of cognate-target genes involves RAR binding at specific response elements and a network of interactions with coregulatory protein complexes. In addition to these classical genomic effects, we recently demonstrated that RA also induces the rapid activation of the p38MAPK/MSK1 pathway, with characteristic downstream consequences on the phosphorylation of RARs and the expression of their target genes. Here, we aimed at deciphering the underlying mechanism of the rapid non-genomic effects of RA. We highlighted a novel paradigm in which a fraction of the cellular RARalpha pool is present in membrane lipid rafts, where it forms complexes with G protein alpha Q (Galphaq) in response to RA. This rapid RA-induced formation of RARalpha/Galphaq complexes in lipid rafts is required for the activation of p38MAPK that occurs in response to RA. Accordingly, in RA-resistant cancer cells, characterized by the absence of p38MAPK activation, RARalpha present in membrane lipid rafts does not associate with Galphaq, pointing out the essential contribution of RARalpha/Galphaq complexes in RA signaling.
Référence
Oncogene. 2012 Jul 12;31(28):3333-45
