TGF-beta-stimulated cooperation of smad proteins with the coactivators CBP/p300

Genes Dev. 1998 Jul 15;12(14):2114-9. doi: 10.1101/gad.12.14.2114.


TGF-beta and activin induce the phosphorylation and activation of Smad2 and Smad3, but how these proteins stimulate gene transcription is poorly understood. We report that TGF-beta receptor phosphorylation of Smad3 promotes its interaction with the paralogous coactivators CBP and p300, whereas CBP/p300 binding to nonphosphorylated Smad3 or its oligomerization partner Smad4 is negatively regulated by Smad-intramolecular interactions. Furthermore, p300 and TGF-beta receptor-phosphorylated Smad3 synergistically augment transcriptional activation. Thus, CBP/p300 are important components of activin/TGF-beta signaling and may mediate the antioncogenic functions of Smad2 and Smad4.

Publication types

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

MeSH terms

  • Animals
  • CREB-Binding Protein
  • Cell Line, Transformed
  • Chromosome Mapping
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Smad2 Protein
  • Smad3 Protein
  • Smad4 Protein
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcriptional Activation*
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Tumor Cells, Cultured


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • SMAD2 protein, human
  • SMAD3 protein, human
  • SMAD4 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Smad4 Protein
  • Trans-Activators
  • Transforming Growth Factor beta
  • CREB-Binding Protein
  • CREBBP protein, human