Fiche publication
Date publication
janvier 2007
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRONEMEYER Hinrich
Tous les auteurs :
Alvarez S, Germain P, Alvarez R, Rodriguez-Barrios F, Gronemeyer H, de Lera AR
Lien Pubmed
Résumé
Only one of the three-retinoic acid receptors, RARbeta, is frequently deleted or epigenetically silenced at early stages in tumor progression and there is compelling evidence that RARbeta corresponds to a tumor suppressor. Recent discoveries may help to reveal the molecular basis of the tumor suppressive action of this retinoic acid receptor subtype and provide new tools for its analysis and, possibly, therapeutic exploitation. The first concerns the recent elucidation of the crystal structure of the ligand-binding domain of the agonist-bound receptor. The second is the discovery of selective agonists, including isoform selective ligands, which are important tools to facilitate the pharmacological analysis of the tumor suppressor function of this protein in vivo. Lastly, its involvement in a retinoic acid-induced tumor-specific apoptosis program mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Herein we describe the structure, function and ligand-dependent transcription mechanism of retinoic acid receptor beta, and use rational drug design to understand the selectivity of these modulators.
Référence
Int J Biochem Cell Biol. 2007;39(7-8):1406-15
