Document Detail


Agonist-dependent repression mediated by mutant estrogen receptor alpha that lacks the activation function 2 core domain.
MedLine Citation:
PMID:  11487586     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nuclear receptor corepressor (N-CoR) and silencing mediator of retinoid and thyroid hormone receptors (SMRT) form heterogeneous complexes with various histone deacetylases (HDACs). In this report, we found that ER alpha-Delta AF2, a mutant estrogen receptor alpha (ER alpha) deleted for the C-terminal activation function 2 (AF2) core domain, directs estradiol (E(2))-dependent repression and impairs E(2)-induced transactivation by wild type ER alpha. This repression required coexpressed BRG1 in SW-13 cells that lack BRG1, the ATPase constituent of the chromatin-remodeling SWI.SNF complex, and was abolished by HDAC inhibitor trichostatin A. We further demonstrated that ER alpha-Delta AF2 constitutively associates with SMRT but binds DNA in an E(2)-dependent manner in vivo. These results suggest that ER alpha-Delta AF2 and similar mutant receptors recently found associated with certain tumors may actively perturb the normal E(2) signaling via SWI/SNF, N-CoR/SMRT, and HDAC.
Authors:
D J Jung; S K Lee; J W Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2001-08-03
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  276     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2001 Oct 
Date Detail:
Created Date:  2001-10-01     Completed Date:  2001-12-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  37280-3     Citation Subset:  IM    
Affiliation:
Center for Ligand and Transcription, Pohang University of Science and Technology, Pohang 790-784, Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Cercopithecus aethiops
DNA / drug effects,  metabolism
DNA Helicases
DNA-Binding Proteins / metabolism
Estradiol / pharmacology
Estrogen Receptor alpha
Gene Deletion
Gene Silencing / physiology*
Histone Deacetylases / physiology
Humans
Mutation
Nuclear Proteins / metabolism,  physiology
Nuclear Receptor Co-Repressor 1
Nuclear Receptor Co-Repressor 2
Protein Structure, Tertiary
Receptors, Estrogen / genetics,  physiology*
Repressor Proteins / metabolism
Signal Transduction
Transcription Factors / physiology
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Estrogen Receptor alpha; 0/NCOR1 protein, human; 0/NCOR2 protein, human; 0/Nuclear Proteins; 0/Nuclear Receptor Co-Repressor 1; 0/Nuclear Receptor Co-Repressor 2; 0/Receptors, Estrogen; 0/Repressor Proteins; 0/Transcription Factors; 50-28-2/Estradiol; 9007-49-2/DNA; EC 3.5.1.98/Histone Deacetylases; EC 3.5.1.98/histone deacetylase 3; EC 3.6.1.-/DNA Helicases; EC 3.6.1.-/SMARCA4 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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