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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
32
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pubmed:dateCreated |
2001-8-6
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pubmed:abstractText |
Using the plasminogen activator inhibitor (PAI) promoter to drive the expression of a reporter gene (mouse CD2), we devised a system to clone negative regulators of the transforming growth factor-beta (TGF-beta) signaling pathway. We infected a TGF-beta-responsive cell line (MvLu1) with a retroviral cDNA library, selecting by fluorescence-activated cell sorter single cells displaying low PAI promoter activity in response to TGF-beta. Using this strategy we cloned the proto-oncogene brain factor-1 (BF-1). BF-1 represses the PAI promoter in part by associating with both unphosphorylated Smad3 (in the cytoplasm) and phosphorylated Smad3 (in the nucleus), thus preventing its binding to DNA. BF-1 also associates with Smad1, -2, and -4; the Smad MH2 domain binds to BF-1, and the C-terminal segment of BF-1 is uniquely and solely required for binding to Smads. Further, BF-1 represses another TGF-beta-induced promoter (p15), it up-regulates a TGF-beta-repressed promoter (Cyclin A), and it reverses the growth arrest caused by TGF-beta. Our results suggest that BF-1 is a general inhibitor of TGF-beta signaling and as such may play a key role during brain development.
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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/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxd1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Madh4 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Smad Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Smad1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad1 protein, mouse,
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/Smad4 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine,
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 |
Aug
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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 |
10
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30224-30
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11387330-3T3 Cells,
pubmed-meshheading:11387330-Animals,
pubmed-meshheading:11387330-Binding Sites,
pubmed-meshheading:11387330-Brain,
pubmed-meshheading:11387330-Cell Separation,
pubmed-meshheading:11387330-Cloning, Molecular,
pubmed-meshheading:11387330-DNA,
pubmed-meshheading:11387330-DNA, Complementary,
pubmed-meshheading:11387330-DNA-Binding Proteins,
pubmed-meshheading:11387330-Flow Cytometry,
pubmed-meshheading:11387330-Forkhead Transcription Factors,
pubmed-meshheading:11387330-Glutathione Transferase,
pubmed-meshheading:11387330-Luciferases,
pubmed-meshheading:11387330-Mice,
pubmed-meshheading:11387330-Microscopy, Fluorescence,
pubmed-meshheading:11387330-Mutation,
pubmed-meshheading:11387330-Nerve Tissue Proteins,
pubmed-meshheading:11387330-Phosphorylation,
pubmed-meshheading:11387330-Promoter Regions, Genetic,
pubmed-meshheading:11387330-Protein Binding,
pubmed-meshheading:11387330-Protein Structure, Tertiary,
pubmed-meshheading:11387330-Recombinant Proteins,
pubmed-meshheading:11387330-Retroviridae,
pubmed-meshheading:11387330-Signal Transduction,
pubmed-meshheading:11387330-Smad Proteins,
pubmed-meshheading:11387330-Smad1 Protein,
pubmed-meshheading:11387330-Smad2 Protein,
pubmed-meshheading:11387330-Smad3 Protein,
pubmed-meshheading:11387330-Smad4 Protein,
pubmed-meshheading:11387330-Thymidine,
pubmed-meshheading:11387330-Trans-Activators,
pubmed-meshheading:11387330-Transfection,
pubmed-meshheading:11387330-Transforming Growth Factor beta,
pubmed-meshheading:11387330-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
Functional cloning of the proto-oncogene brain factor-1 (BF-1) as a Smad-binding antagonist of transforming growth factor-beta signaling.
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pubmed:affiliation |
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, 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
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