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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
47
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pubmed:dateCreated |
1999-12-14
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pubmed:databankReference |
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pubmed:abstractText |
Smad7 is a regulatory Smad protein that is able to antagonize signal transduction by transforming growth factor-beta (TGF-beta) and activin receptors. To characterize the regulation of Smad7 at the transcriptional level, we isolated the promoter region of the mouse Smad7 gene. When the Smad7 promoter luciferase reporter gene (-408 and +112 bp) was expressed in human hepatoma (HepG2) cells, its transcriptional activity was increased following TGF-beta or activin treatment. In addition, this region of the Smad7 promoter was stimulated by ectopic expression of Smad3 as well as constitutively active TGF-beta and activin receptors, indicating that Smad7 transcription was modulated by the signaling downstream those two receptors. A gel mobility shift assay indicated that a DNA fragment spanning -408 to -126 base pairs (bp) was able to directly bind purified Smad4. Furthermore, a consensus Smad3-Smad4 binding element (SBE) was discovered in this region of the promoter with a palindromic sequence of GTCTAGAC. A 33-bp Smad7 promoter fragment containing this SBE was able to bind Smad3 and Smad4. In human embryonic kidney 293 cells, the expression of constitutively active TGF-beta type I receptor was able to induce the formation of a Smad3- and Smad4-containing nuclear protein complex that bound the SBE. In HepG2 cells, TGF-beta1 treatment could induce the formation of an endogenous SBE-binding complex. Taken together, these data provided the first evidence that Smad7 transcription is regulated by TGF-beta and activin signaling through direct binding of Smad3 and Smad4 to the Smad7 promoter.
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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/Activins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Smad4 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Smad7 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad7 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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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 |
19
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pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
33412-8
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10559222-Activins,
pubmed-meshheading:10559222-Animals,
pubmed-meshheading:10559222-Base Sequence,
pubmed-meshheading:10559222-Cell Line,
pubmed-meshheading:10559222-DNA,
pubmed-meshheading:10559222-DNA-Binding Proteins,
pubmed-meshheading:10559222-Humans,
pubmed-meshheading:10559222-Inhibins,
pubmed-meshheading:10559222-Mice,
pubmed-meshheading:10559222-Molecular Sequence Data,
pubmed-meshheading:10559222-Promoter Regions, Genetic,
pubmed-meshheading:10559222-Protein Binding,
pubmed-meshheading:10559222-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:10559222-Smad3 Protein,
pubmed-meshheading:10559222-Smad4 Protein,
pubmed-meshheading:10559222-Smad7 Protein,
pubmed-meshheading:10559222-Trans-Activators,
pubmed-meshheading:10559222-Transcription, Genetic,
pubmed-meshheading:10559222-Transforming Growth Factor beta,
pubmed-meshheading:10559222-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
Regulation of Smad7 promoter by direct association with Smad3 and Smad4.
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pubmed:affiliation |
Department of Medical Genetics, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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