The retinoid X receptor ligand restores defective signalling by the vitamin D receptor

EMBO Rep. 2006 Oct;7(10):1030-4. doi: 10.1038/sj.embor.7400776. Epub 2006 Aug 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alitretinoin
  • Cell Differentiation / drug effects
  • Dimerization
  • Histone Acetyltransferases / metabolism
  • Humans
  • Ligands*
  • Mutant Proteins / metabolism
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 2 / metabolism
  • Nuclear Receptor Coactivator 3
  • Protein Binding
  • Receptors, Calcitriol / metabolism*
  • Retinoid X Receptors / agonists
  • Retinoid X Receptors / metabolism*
  • Signal Transduction*
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Tretinoin / pharmacology
  • Tumor Cells, Cultured


  • Ligands
  • Mutant Proteins
  • NCOA2 protein, human
  • Nuclear Receptor Coactivator 2
  • Receptors, Calcitriol
  • Retinoid X Receptors
  • Trans-Activators
  • Transcription Factors
  • Alitretinoin
  • Tretinoin
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • NCOA3 protein, human
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 3