Individual subunits of heterodimers comprised of retinoic acid and retinoid X receptors interact with their ligands independently.

The retinoid X receptor (RXR) is a member of a family of transcription factors, known as hormone nuclear receptors, that mediate the effects of hydrophobic hormones on gene transcription. RXR, which is activated by 9-cis-retinoic acid (9cRA), can modulate several signaling pathways by virtue of its ability to form heterodimers with other members of the receptor family, as, for example, the retinoic acid receptor (RAR). The roles of the individual receptors within heterodimers are not clear as yet. It was recently reported that heterodimerization inhibits transcriptional activation by RXR, an effect that was attributed to an inability of RXR within heterodimers to bind its ligand. This inhibition was reported to depend on the association of heterodimers with cognate DNA and on the level of saturation of the RAR subunit within the heterodimers. In the present work, the ligand-binding characteristics of RXR and RAR individually and within heterodimers were examined by fluorescence-based methods. The results indicate that heterodimerization with RAR does ot alter the ligand-binding capacity of RXR nor the rate of dissociation of the ligand from this receptor. The ligand-binding capacity of RXR also was not affected by association of heterodimers with cognate DNA nor by the level of saturation of the RAR subunit. The data indicate further that the affinity of RAR for 9cRA is considerably higher as compared to RXR and that this differential affinity is retained within RAR-RXR heterodimers. Thus, binding of ligands by subunits within RAR-RXR heterodimers proceeds independently.