rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2004-9-22
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pubmed:abstractText |
Although several lines of evidence have indicated that the activity of SRC-3/AIB1/ACTR/pCIP/RAC3/TRAM1 could be regulated by phosphorylation, an important question remained as to how different signaling pathways can act through limiting concentrations of the same SRC-3 molecule to exert different physiological functions. Herein, we report the successful identification of six functional in vivo SRC-3 phosphorylation sites. Interestingly, all phosphorylation sites are required for coactivation of estrogen and androgen receptors, but not all sites are required for coactivation of NF-kappaB. Different combinations of site-specific phosphorylations of SRC-3 are required for induction of IL-6 gene expression by TNF-alpha as compared to oncogenic transformation of MEFs. Mechanisms of pathway selectivity involve protein-protein interactions of differentially phosphorylated SRC-3 with downstream transcriptional activators and coactivators. Our results uncovered an additional level of transcriptional regulation whereby specific modulations of SRC-3 phosphorylation allow this coactivator to function as a regulatable integrator for diverse signaling pathways in cells.
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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/Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/NCOA3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ncoa3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Coactivator 3,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
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 |
Sep
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2004 Cell Press
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
937-49
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15383283-Acetyltransferases,
pubmed-meshheading:15383283-Animals,
pubmed-meshheading:15383283-Blotting, Western,
pubmed-meshheading:15383283-Cell Line,
pubmed-meshheading:15383283-Cell Line, Tumor,
pubmed-meshheading:15383283-Fibroblasts,
pubmed-meshheading:15383283-Genome,
pubmed-meshheading:15383283-Glutathione,
pubmed-meshheading:15383283-HeLa Cells,
pubmed-meshheading:15383283-Histone Acetyltransferases,
pubmed-meshheading:15383283-Humans,
pubmed-meshheading:15383283-Mice,
pubmed-meshheading:15383283-Nuclear Receptor Coactivator 3,
pubmed-meshheading:15383283-Oncogene Proteins,
pubmed-meshheading:15383283-Phosphorylation,
pubmed-meshheading:15383283-Precipitin Tests,
pubmed-meshheading:15383283-RNA, Small Interfering,
pubmed-meshheading:15383283-Recombinant Fusion Proteins,
pubmed-meshheading:15383283-Retroviridae,
pubmed-meshheading:15383283-Signal Transduction,
pubmed-meshheading:15383283-Trans-Activators,
pubmed-meshheading:15383283-Transcription Factors
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pubmed:year |
2004
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pubmed:articleTitle |
Selective phosphorylations of the SRC-3/AIB1 coactivator integrate genomic reponses to multiple cellular signaling pathways.
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pubmed:affiliation |
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, 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.
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