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

Abstract
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.
AuthorsRuth Sánchez-Martínez, Ana I Castillo, Andreas Steinmeyer, Ana Aranda
JournalEMBO reports (EMBO Rep) Vol. 7 Issue 10 Pg. 1030-4 (Oct 2006) ISSN: 1469-221X [Print] England
PMID16936639 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 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
Topics
  • 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, metabolism)
  • Signal Transduction
  • Trans-Activators (metabolism)
  • Transcription Factors (metabolism)
  • Transcriptional Activation
  • Tretinoin (pharmacology)
  • Tumor Cells, Cultured

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