A Smad transcriptional corepressor.
Following TGFbeta receptor-mediated phosphorylation and association with Smad4, Smad2 moves into the nucleus, binds to target promoters in association with DNA-binding cofactors, and recruits coactivators such as p300/CBP to activate transcription. We identified the homeodomain protein TGIF as a Smad2-binding protein and a repressor of transcription. A TGFbeta-activated Smad complex can recruit TGIF and histone deacetylases (HDACs) to a Smad target promoter, repressing transcription. Thus, upon entering the nucleus, a Smad2-Smad4 complex may interact with coactivators, forming a transcriptional activation complex, or with TGIF and HDACs, forming a transcriptional repressor complex. Formation of one of these two mutually exclusive complexes is determined by the relative levels of Smad corepressors and coactivators within the cell.
Wotton
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Cell Biology Program, Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
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Lee
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Massagué
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D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004847:Epithelial Cells; D051858:Forkhead Transcription Factors; D006655:Histone Deacetylases / Q000378:metabolism / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology*; D008168:Lung; D046911:Macromolecular Substances; D008907:Mink; D009687:Nuclear Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D015398:Signal Transduction; D051899:Smad2 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C491117:Foxh1 protein, mouse; D018398:Homeodomain Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D012097:Repressor Proteins; D051899:Smad2 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D006655:Histone Deacetylases