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 RXRα (ref. 11) is one of these nuclear proteins. RXRα 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 RXRα can greatly enhance the transcriptional activity of TR and RAR at low retinoic acid concentrations that do not significantly activate RXRα itself. Thus, RXRα 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.