1. ¹Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 10142, 67404 Illkirch Cedex, France
2. ²Laboratorio di Biologia Molecolare, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milano, Italy

Correspondence: C Rochette-Egly, IGBMC, BP 10142, 67404 Illkirch Cedex, CU de Strasbourg, France. E-mail: cegly@igbmc.u-strasbg.fr

³Current address: Laboratoire de Neurogénétique Moléculaire, INSERM E.0223, Génopole, 2 rue Gaston Crémieux, 91057 Evry Cedex, France

⁴Current address: Cancer Research UK, Signal Transduction Laboratory, 44 Lincoln's Inn Field, London WC2A3PX, UK

Received 25 February 2004; Revised 28 October 2004; Accepted 25 November 2004; Published online 31 January 2005.

Abstract

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 RXR, 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 RXR and apoptosis. Taking advantage of 'rescue' F9 cell lines expressing RXR mutated at its phosphorylation sites, in an RXR null background, we provide evidence that RXR is a key element involved in that potentiating effect. Finally, we demonstrate that As₂O₃ also abrogates the transactivation of RA-target genes.