FORMATION OF RETINOID-X RECEPTOR HOMODIMERS LEADS TO REPRESSION OF T(3) RESPONSE - HORMONAL CROSS-TALK BY LIGAND-INDUCED SQUELCHING

Thyroid hormone receptors (TRs) form heterodimers with retinoid X rece ptors (RXRs). Heterodimerization is required for efficient TR DNA bind ing to most response elements and transcriptional activation by thyroi d hormone. RXRs also function as auxiliary proteins for several other receptors. In addition, RXRalpha can be induced by specific ligands to form homodimers. Here we report that RXR-specific retinoids that indu ce RXR homodimers are effective repressors of the T3 response. We prov ide evidence that this repression by RXR-specific ligands occurs by se questering of RXR from TR-RXR heterodimers into RXR homodimers. This l igand-induced squelching may represent an important mechanism by which RXR-specific retinoids and 9-cis retinoic acid mediate hormonal cross talk among a subfamily of nuclear receptors activated by structurally unrelated ligands.