The retinoid X receptor ligand restores defective signalling by the vitamin D receptor.
It is assumed that the retinoid X receptor (RXR) acts as a silent partner to the vitamin D receptor ( VDR) with its only function to increase affinity of VDR/RXR to its DNA recognition site. In this study, we show that the RXR ligand 9-cis-retinoic acid (9-cis-RA) induces recruitment of coactivators by the DNA-bound heterodimer and potentiates vitamin D-dependent transcriptional responses. The presence of 9-cis-RA increases induction of cyp24 transcripts and differentiation of colon cancer cells by vitamin D, confers significant agonistic activity to a VDR ligand with very low agonistic activity and can even restore transcriptional activity of an AF-2 mutant VDR that causes hereditary rickets. This study shows that, in VDR/RXR heterodimers, allosteric communication triggered by the RXR ligand has a previously unrecognized role in vitamin D signalling, with important physiological and therapeutic implications.[1]References
- The retinoid X receptor ligand restores defective signalling by the vitamin D receptor. S??nchez-Mart??nez, R., Castillo, A.I., Steinmeyer, A., Aranda, A. EMBO Rep. (2006) [Pubmed]
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