Retinoic acid and arsenic trioxide cooperate for apoptosis through phosphorylated RXR alpha.
Fiche publication
Date publication
mars 2005
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ROCHETTE-EGLY Cécile
Tous les auteurs :
Tarrade A, Bastien J, Bruck N, Bauer A, Gianni M, Rochette-Egly C
Lien Pubmed
Résumé
Arsenite trioxide (As2O3) induces apoptosis in several cell lines by disturbing key signal transduction pathways through its oxidative properties. Here, we report that As2O3 also induces the phosphorylation of the retinoid receptor RXRalpha, subsequent to oxidative damages and the activation of the stress-activated protein kinases cascade (JNKs). We also report that RA amplifies both As2O3-induced phosphorylation of RXRalpha and apoptosis. Taking advantage of 'rescue' F9 cell lines expressing RXRalpha mutated at its phosphorylation sites, in an RXRalpha null background, we provide evidence that RXRalpha is a key element involved in that potentiating effect. Finally, we demonstrate that As2O3 also abrogates the transactivation of RA-target genes.
Référence
Oncogene. 2005 Mar 31;24(14):2277-88.