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rdf:type |
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lifeskim:mentions |
umls-concept:C0024660,
umls-concept:C0086860,
umls-concept:C0376315,
umls-concept:C0376571,
umls-concept:C0439855,
umls-concept:C0449432,
umls-concept:C0851285,
umls-concept:C1179435,
umls-concept:C1335840,
umls-concept:C1336789,
umls-concept:C1524073,
umls-concept:C1548534,
umls-concept:C1548799,
umls-concept:C1705248
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pubmed:issue |
20
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pubmed:dateCreated |
2003-5-12
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pubmed:abstractText |
Ets-2 is a transcriptional activator that can be modulated by ras-dependent phosphorylation. Evidence is presented indicating that ets-2 can also act as a transcriptional repressor. In the breast cancer cell line MCF-7, exogenous ets-2 repressed the activity of a BRCA1 promoter-luciferase reporter dependent on a conserved ets-2-binding site in this promoter. Conditional overproduction of ets-2 in MCF-7 cells resulted in repression of endogenous BRCA1 mRNA expression. To address the mechanism by which ets-2 could act as a repressor, a biochemical approach was used to identify proteins that interacted with the ets-2 pointed domain. From this analysis, components of the mammalian SWI/SNF chromatin remodeling complex were found to interact with ets-2. Brg-1, the ATP-hydrolyzing component of the SWI/SNF complex, along with the BAF57/p50 and Ini1 subunits could be co-immunoprecipitated from cells with ets-2. The pointed domain of ets-2 directly interacted in vitro with the C-terminal region of Brg-1 in a phosphorylation-dependent manner. The combination of Brg-1 and ets-2 could repress the BRCA1 promoter reporter in transfection assays. These results support a role for ets-2 as a repressor and indicate that components of the mammalian SNF/SWI complex are required as co-repressors.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Helicases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ERF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ETS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ets2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Protein c-ets-2,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SMARCA4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smarca4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17876-84
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12637547-3T3 Cells,
pubmed-meshheading:12637547-Adenosine Triphosphate,
pubmed-meshheading:12637547-Animals,
pubmed-meshheading:12637547-Base Sequence,
pubmed-meshheading:12637547-Blotting, Northern,
pubmed-meshheading:12637547-Blotting, Western,
pubmed-meshheading:12637547-Chromatin,
pubmed-meshheading:12637547-DNA Helicases,
pubmed-meshheading:12637547-DNA-Binding Proteins,
pubmed-meshheading:12637547-Gene Expression Regulation,
pubmed-meshheading:12637547-Genes, BRCA1,
pubmed-meshheading:12637547-Humans,
pubmed-meshheading:12637547-Hydrolysis,
pubmed-meshheading:12637547-Luciferases,
pubmed-meshheading:12637547-Mice,
pubmed-meshheading:12637547-Molecular Sequence Data,
pubmed-meshheading:12637547-Nuclear Proteins,
pubmed-meshheading:12637547-Phosphorylation,
pubmed-meshheading:12637547-Precipitin Tests,
pubmed-meshheading:12637547-Promoter Regions, Genetic,
pubmed-meshheading:12637547-Protein Binding,
pubmed-meshheading:12637547-Protein Structure, Tertiary,
pubmed-meshheading:12637547-Proto-Oncogene Protein c-ets-2,
pubmed-meshheading:12637547-Proto-Oncogene Proteins,
pubmed-meshheading:12637547-Recombinant Proteins,
pubmed-meshheading:12637547-Repressor Proteins,
pubmed-meshheading:12637547-Trans-Activators,
pubmed-meshheading:12637547-Transcription Factors,
pubmed-meshheading:12637547-Transfection,
pubmed-meshheading:12637547-Tumor Cells, Cultured
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pubmed:year |
2003
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pubmed:articleTitle |
Ets-2 and components of mammalian SWI/SNF form a repressor complex that negatively regulates the BRCA1 promoter.
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pubmed:affiliation |
Department of Molecular Genetics and The Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 43210, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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