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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2002-3-4
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pubmed:abstractText |
ERalpha is a ligand-activated transcription factor and a key regulator of the processes involved in cellular proliferation and differentiation. In addition, aberrant ERalpha activity is linked to several pathological conditions including breast cancer. A complex network of coregulatory proteins is largely believed to determine the transcriptional activity of ERalpha. We report here the isolation of a protein, denoted RTA for repressor of tamoxifen transcriptional activity, which contains an RNA recognition motif and interacts with the receptor N-terminal activation domain. RTA interacts with RNA in vitro, and its overexpression inhibits the partial agonist activity manifest by the antiestrogen tamoxifen while minimally affecting E2-activated transcription. Mutation of the RNA recognition motif alters RNA binding specificity and results in a dominant negative form of RTA that leads to derepression of ERalpha transcriptional activity, allowing all classes of antiestrogens to manifest partial agonist activity and enhancing agonist efficacy. These findings suggest a role for RNA binding proteins as coregulatory factors of the nuclear receptor family and reveal a novel mechanism by which antiestrogens can manifest agonist activities in some tissues.
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pubmed:grant |
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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 |
Mar
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pubmed:issn |
0888-8809
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
459-68
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pubmed:dateRevised |
2011-10-10
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pubmed:meshHeading |
pubmed-meshheading:11875103-Amino Acid Sequence,
pubmed-meshheading:11875103-Binding Sites,
pubmed-meshheading:11875103-Blotting, Northern,
pubmed-meshheading:11875103-Consensus Sequence,
pubmed-meshheading:11875103-Estradiol,
pubmed-meshheading:11875103-Estrogen Antagonists,
pubmed-meshheading:11875103-Estrogen Receptor alpha,
pubmed-meshheading:11875103-Gene Expression,
pubmed-meshheading:11875103-HeLa Cells,
pubmed-meshheading:11875103-Humans,
pubmed-meshheading:11875103-Molecular Sequence Data,
pubmed-meshheading:11875103-Mutagenesis,
pubmed-meshheading:11875103-RNA,
pubmed-meshheading:11875103-RNA-Binding Proteins,
pubmed-meshheading:11875103-Receptors, Estrogen,
pubmed-meshheading:11875103-Repressor Proteins,
pubmed-meshheading:11875103-Tamoxifen,
pubmed-meshheading:11875103-Tissue Distribution,
pubmed-meshheading:11875103-Transcription, Genetic,
pubmed-meshheading:11875103-Transfection,
pubmed-meshheading:11875103-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
A negative coregulator for the human ER.
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pubmed:affiliation |
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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