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Vol. 12, No. 14, pp. 2114-2119, July 15, 1998
-stimulated cooperation of Smad proteins with the
coactivators CBP/p300
Molecular Biology and Virology Laboratory, The Salk
Institute, La Jolla, California 92037 USA
TGF-
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- 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- receptor-phosphorylated Smad3 synergistically augment transcriptional activation. Thus, CBP/p300 are important components of
activin/TGF- signaling and may mediate the
antioncogenic functions of Smad2 and Smad4.
[Key Words:
CBP; p300; phosphorylation; Smad protein; TGF-; transcription]
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