TGF-β-stimulated cooperation of Smad proteins with the coactivators CBP/p300
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.
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Footnotes
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↵1 Corresponding author.
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E-MAIL rjanknecht{at}aim.salk.edu; FAX 619-457-4765.
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- Received April 22, 1998.
- Accepted June 16, 1998.
- Cold Spring Harbor Laboratory Press
