Retinoic acid and arsenic trioxide cooperate for apoptosis through phosphorylated RXR alpha.
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.
Tarrade
Anne
A
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 10142, 67404 Illkirch Cedex, France.
Bastien
Julie
J
Bruck
Nathalie
N
Bauer
Annie
A
Gianni
Maurizio
M
Rochette-Egly
Cécile
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D017931:DNA Primers; D019281:Dimerization; D051379:Mice; D010087:Oxides / Q000494:pharmacology*; D010766:Phosphorylation; D010957:Plasmids; D047490:Retinoid X Receptor alpha / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology*
D001152:Arsenicals; D017931:DNA Primers; D010087:Oxides; D047490:Retinoid X Receptor alpha; D014212:Tretinoin; D000077237:Arsenic Trioxide