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.
Mesh Terms:
Animals, Binding, Competitive, COS Cells, Cells, Cultured, DNA-Binding Proteins, Epithelial Cells, Forkhead Transcription Factors, Histone Deacetylases, Homeodomain Proteins, Lung, Macromolecular Substances, Mink, Nuclear Proteins, Repressor Proteins, Signal Transduction, Smad2 Protein, Trans-Activators, Transcription Factors, Transcription, Genetic, Transforming Growth Factor beta
Animals, Binding, Competitive, COS Cells, Cells, Cultured, DNA-Binding Proteins, Epithelial Cells, Forkhead Transcription Factors, Histone Deacetylases, Homeodomain Proteins, Lung, Macromolecular Substances, Mink, Nuclear Proteins, Repressor Proteins, Signal Transduction, Smad2 Protein, Trans-Activators, Transcription Factors, Transcription, Genetic, Transforming Growth Factor beta
Cell
Date: Apr. 02, 1999
PubMed ID: 10199400
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