Source:http://linkedlifedata.com/resource/pubmed/id/16224064
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2005-11-14
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| pubmed:abstractText |
Transforming growth factor (TGF)-beta1 is an important cytokine involved in various diseases. However, the molecular mechanism whereby TGF-beta1 signaling modulates the regulatory network for smooth muscle gene transcription remains largely unknown. To address this question, we previously identified a Smad-binding element (SBE) in the SM22alpha promoter as one of the TGF-beta1 response elements. Here, we show that mutation of the SBE reduces the activation potential of a SM22alpha promoter in transgenic mice during embryogenesis. Chromatin immunoprecipitation assays reveal that TGF-beta1 induces Smad3 binding to the SM22alpha promoter in vivo. A multimerized SBE promoter responsive to TGF-beta1 signaling is highly activated by Smad3 but not by the closely related Smad2. Intriguingly, myocardin (Myocd), a known CArG box-dependent serum response factor coactivator, participates in Smad3-mediated TGF-beta1 signaling and synergistically stimulates Smad3-induced SBE promoter activity independent of the CArG box; no such synergy is seen with Smad2. Importantly, Myocd cooperates with Smad3 to activate the wild-type SM22alpha, SM myosin heavy chain, and SMalpha-actin promoters; they also activate the CArG box-mutated SM22alpha promoter as well as the CArG box-independent aortic carboxypeptidase-like protein promoter. Immunopreciptiation assays reveal that Myocd and Smad3 directly interact both in vitro and in vivo. Mutagenesis studies indicate that the C-terminal transactivation domains of Myocd and Smad3 are required for their functional synergy. These results reveal a novel regulatory mechanism whereby Myocd participates in TGF-beta1 signal pathway through direct interaction with Smad3, which binds to the SBEs. This is the first demonstration that Myocd can act as a transcriptional coactivator of the smooth muscle regulatory network in a CArG box-independent manner.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serum Response Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tgfb1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/myocardin,
http://linkedlifedata.com/resource/pubmed/chemical/transgelin
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
1524-4571
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
11
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| pubmed:volume |
97
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
983-91
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| pubmed:dateRevised |
2011-11-10
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| pubmed:meshHeading |
pubmed-meshheading:16224064-Animals,
pubmed-meshheading:16224064-Binding Sites,
pubmed-meshheading:16224064-Gene Expression Regulation,
pubmed-meshheading:16224064-Mice,
pubmed-meshheading:16224064-Mice, Inbred C57BL,
pubmed-meshheading:16224064-Microfilament Proteins,
pubmed-meshheading:16224064-Muscle Proteins,
pubmed-meshheading:16224064-Nuclear Proteins,
pubmed-meshheading:16224064-Promoter Regions, Genetic,
pubmed-meshheading:16224064-Response Elements,
pubmed-meshheading:16224064-Serum Response Factor,
pubmed-meshheading:16224064-Signal Transduction,
pubmed-meshheading:16224064-Smad2 Protein,
pubmed-meshheading:16224064-Smad3 Protein,
pubmed-meshheading:16224064-Trans-Activators,
pubmed-meshheading:16224064-Transcription, Genetic,
pubmed-meshheading:16224064-Transforming Growth Factor beta,
pubmed-meshheading:16224064-Transforming Growth Factor beta1
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| pubmed:year |
2005
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| pubmed:articleTitle |
Myocardin enhances Smad3-mediated transforming growth factor-beta1 signaling in a CArG box-independent manner: Smad-binding element is an important cis element for SM22alpha transcription in vivo.
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| pubmed:affiliation |
Department of Internal Medicine, Wayne State University, Detroit, Michigan, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|