Premium
The retinoid X receptor ligand restores defective signalling by the vitamin D receptor
Author(s) -
SánchezMartínez Ruth,
Castillo Ana I,
Steinmeyer Andreas,
Aranda Ana
Publication year - 2006
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400776
Subject(s) - calcitriol receptor , retinoid x receptor , retinoic acid , allosteric regulation , retinoid x receptor alpha , retinoid , receptor , nuclear receptor , biology , ligand (biochemistry) , vitamin , microbiology and biotechnology , chemistry , endocrinology , transcription factor , medicine , biochemistry , gene
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.