A Smad Transcriptional Corepressor

Cell. 1999 Apr 2;97(1):29-39. doi: 10.1016/s0092-8674(00)80712-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • COS Cells
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Epithelial Cells
  • Forkhead Transcription Factors
  • Histone Deacetylases / metabolism
  • Histone Deacetylases / physiology
  • Homeodomain Proteins / physiology*
  • Lung
  • Macromolecular Substances
  • Mink
  • Nuclear Proteins / physiology
  • Repressor Proteins / physiology*
  • Signal Transduction
  • Smad2 Protein
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Transcription Factors / physiology
  • Transcription, Genetic
  • Transforming Growth Factor beta / physiology

Substances

  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxh1 protein, mouse
  • Homeodomain Proteins
  • Macromolecular Substances
  • Nuclear Proteins
  • Repressor Proteins
  • Smad2 Protein
  • Trans-Activators
  • Transcription Factors
  • Transforming Growth Factor beta
  • Histone Deacetylases