TGF-β-stimulated cooperation of Smad proteins with the coactivators CBP/p300 (original) (raw)

1. Ralf Janknecht1,
2. Nicholas J. Wells, and
3. Tony Hunter
4. Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla, California 92037 USA

Abstract

TGF-β 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-β 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-β receptor-phosphorylated Smad3 synergistically augment transcriptional activation. Thus, CBP/p300 are important components of activin/TGF-β signaling and may mediate the antioncogenic functions of Smad2 and Smad4.

• CBP
• p300
• phosphorylation
• Smad protein
• TGF-β
• transcription

Footnotes

• ↵1 Corresponding author.

• E-MAIL rjanknecht{at}aim.salk.edu; FAX 619-457-4765.

• • Received April 22, 1998.
  • Accepted June 16, 1998.

• Cold Spring Harbor Laboratory Press

•