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.
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Authors | Ruth Sánchez-Martínez, Ana I Castillo, Andreas Steinmeyer, Ana Aranda |
Journal | EMBO reports
(EMBO Rep)
Vol. 7
Issue 10
Pg. 1030-4
(Oct 2006)
ISSN: 1469-221X [Print] England |
PMID | 16936639
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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
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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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