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Genes Dev. 1998 Jul 15;12(14):2114-9.

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

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  • 1Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla, California 92037 USA. rjanknecht@aim.salk.edu


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.

[PubMed - indexed for MEDLINE]
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