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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6497
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pubmed:dateCreated |
1994-10-31
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pubmed:abstractText |
Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) regulate transcription by binding to response elements in target genes that generally consist of two direct repeat half-sites of consensus sequence AGGTCA (ref. 1). RAR/RXR heterodimers activate transcription in response to all-trans or 9-cis retinoic acid by binding to direct repeats spaced by five base pairs (DR5 elements), such that RAR occupies the downstream half-site. RXR homodimers activate transcription in response to 9-cis retinoic acid by binding to direct repeats spaced by one base pair (DR1 elements). Although RXR/RAR heterodimers bind to DR1 elements with higher affinity than RXR homodimers, in most contexts they are unable to activate transcription in response to either all-trans or 9-cis retinoic acid. As a result, RARs inhibit RXR-dependent transcription from these sites. We report that the switching of the RAR from an activator to an inhibitor of retinoid-dependent transcription requires that it be bound to the upstream half-site of DR1 elements and that it allosterically block the binding of ligand to the RXR.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0028-0836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
371
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
528-31
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7935766-Allosteric Regulation,
pubmed-meshheading:7935766-Base Sequence,
pubmed-meshheading:7935766-Cell Line,
pubmed-meshheading:7935766-DNA,
pubmed-meshheading:7935766-Escherichia coli,
pubmed-meshheading:7935766-Humans,
pubmed-meshheading:7935766-Ligands,
pubmed-meshheading:7935766-Molecular Sequence Data,
pubmed-meshheading:7935766-Protein Binding,
pubmed-meshheading:7935766-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:7935766-Receptors, Retinoic Acid,
pubmed-meshheading:7935766-Recombinant Fusion Proteins,
pubmed-meshheading:7935766-Repetitive Sequences, Nucleic Acid,
pubmed-meshheading:7935766-Retinoid X Receptors,
pubmed-meshheading:7935766-Signal Transduction,
pubmed-meshheading:7935766-Transcription, Genetic,
pubmed-meshheading:7935766-Transcription Factors
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pubmed:year |
1994
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pubmed:articleTitle |
Regulation of retinoid signalling by receptor polarity and allosteric control of ligand binding.
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pubmed:affiliation |
Division of Cellular and Molecular Medicine, University of California, San Diego 92093-0656.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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