RXRα, a promiscuous partner of retinoic acid thyroid hormone receptors

Retinoic acid receptor (RAR), thyroid hormone receptor (T₃R) and vitamin D₃ receptor (VD₃R) differ from steroid hormone receptors in that they bind and transactivate through responsive elements organized as direct rather than inverted repeats. We now show that recombinant RAR and T₃R are monomers in solution and cannot form stable homodimeric complexes on their responsive elements. Stable binding of the receptors to their responsive elements requires heterodimerization with a nuclear factor. This auxiliary factor is tightly associated with RAR and T₃R in the absence of DNA and co-purifies with both receptors. As demonstrated by extensive purification, the same auxiliary factor is required for stable DNA binding of RAR as for that of T₃R; the factor also facilitates the formation of a stable VD₃R-DNA complex. The auxiliary factor is identical to the retinoid X receptor α (RXRα) by biochemical and functional criteria. The identification of RXRα as a dimerization partner for the RARs, T₃Rs and VD₃R has important implications as to the function of these receptors and their ligands in development, homeostasis and neoplasia.