Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors

THYROID hormones and retinoic acid function through nuclear receptors that belong to the steroid/thyroid-hormone receptor superfamily (reviewed in refs 1-4). Thyroid hormone receptors (TRs) and retinoic acid receptors (RARs) require auxiliary nuclear proteins for efficient DNA binding 5-10. Here we report that retinoid X receptors RXR-alpha (ref. 11) is one of these nuclear proteins. RXR-alpha interacts both with TRs and with RARs, forming heterodimers in solution that strongly interact with a variety of T3/retinoic acid response elements. Transfection experiments show that RXR-alpha can greatly enhance the transcriptional activity of TR and RAR at low retinoic acid concentrations that do not significantly activate RXR-alpha itself. Thus, RXR-alpha enhances the transcriptional activity of other receptors and its own ligand sensitivity by heterodimer formation. Our studies reveal a new subclass of receptors and a regulatory pathway controlling nuclear receptor activities by heterodimer formation.