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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
26
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pubmed:dateCreated |
2004-6-21
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pubmed:abstractText |
Deregulation of c-myc expression is implicated in the pathogenesis of many neoplasias. Estrogen receptor alpha (ERalpha) can increase the rate of c-myc transcription through the recruitment of a variety of cofactors to the promoter, yet the precise roles of these cofactors in transcription and tumorigenesis are largely unknown. We show here that a putative tumor suppressor TIP30, also called CC3 or Htatip2, interacts with an ERalpha-interacting coactivator CIA. Using chromatin immunoprecipitation assays, we demonstrate that TIP30 and CIA are distinct cofactors that are dynamically associated with the promoter and downstream regions of the c-myc gene in response to estrogen. Both TIP30 and CIA are recruited to the c-myc gene promoter by liganded ERalpha in the second transcription cycle. TIP30 overexpression represses ERalpha-mediated c-myc transcription, whereas TIP30 deficiency enhances c-myc transcription in both the absence and presence of estrogen. Ectopic CIA cooperates with TIP30 to repress ERalpha-mediated c-myc transcription. Moreover, virgin TIP30 knockout mice exhibit increased c-myc expression in mammary glands. Together, these results reveal an important role for TIP30 in the regulation of ERalpha-mediated c-myc transcription and suggest a mechanism for tumorigenesis promoted by TIP30 deficiency.
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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/Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogen Receptor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/HTATIP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NCOA5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Coactivators,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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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 |
25
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
27781-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15073177-Acetyltransferases,
pubmed-meshheading:15073177-Animals,
pubmed-meshheading:15073177-COS Cells,
pubmed-meshheading:15073177-Cercopithecus aethiops,
pubmed-meshheading:15073177-Estrogen Receptor alpha,
pubmed-meshheading:15073177-Exons,
pubmed-meshheading:15073177-Female,
pubmed-meshheading:15073177-Genes, myc,
pubmed-meshheading:15073177-HeLa Cells,
pubmed-meshheading:15073177-Humans,
pubmed-meshheading:15073177-Mammary Glands, Animal,
pubmed-meshheading:15073177-Mice,
pubmed-meshheading:15073177-Mice, Inbred C57BL,
pubmed-meshheading:15073177-Mice, Knockout,
pubmed-meshheading:15073177-Nuclear Receptor Coactivators,
pubmed-meshheading:15073177-Precipitin Tests,
pubmed-meshheading:15073177-Promoter Regions, Genetic,
pubmed-meshheading:15073177-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:15073177-Receptors, Estrogen,
pubmed-meshheading:15073177-Recombinant Proteins,
pubmed-meshheading:15073177-Transcription, Genetic,
pubmed-meshheading:15073177-Transcription Factors,
pubmed-meshheading:15073177-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
TIP30 interacts with an estrogen receptor alpha-interacting coactivator CIA and regulates c-myc transcription.
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pubmed:affiliation |
Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha 68198-7696, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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