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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.

Pubmed ID: 10199400


  • Wotton D
  • Lo RS
  • Lee S
  • Massagu√© J



Publication Data

April 2, 1999

Associated Grants

  • Agency: NCI NIH HHS, Id: CA34610
  • Agency: NIGMS NIH HHS, Id: GM07739

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