HOMODIMER FORMATION OF RETINOID X-RECEPTOR INDUCED BY 9-CIS RETINOIC ACID

RETINOID response pathways are mediated by two classes of receptors, the retinoic acid receptors (RARs)1-6 and the retinoid X receptors (RXRs)7-11. A central question is whether distinct response pathways are regulated by these two classes of receptors. The observation that the stereoisomer 9-cis-retinoic acid binds with high affinity to RXRs12,13 suggested that this retinoid has a distinct role in controlling RXR activity, but it was almost simultaneously discovered that RXRs function as auxiliary receptors for RARs and related receptors, and are essential for DNA binding and function of those receptors9,10,14-17. Hence, although RARs seem to operate effectively only as heterodimeric RAR/RXR complexes, RXRs themselves apparently function predominantly, if not exclusively, as auxiliary receptors. Here we report that 9-cis-retinoic acid induces RXR homodimer formation. Our results demonstrate a new mechanism for retinoid action by which a ligand-induced homodimer mediates a distinct retinoid response pathway.