TGF-BETA-STIMULATED COOPERATION OF SMAD PROTEINS WITH THE COACTIVATORS CBP P300/

TGE-beta and activin induce the phosphorylation and activation of Smad 2 and Smad3, but how these proteins stimulate gene transcription is po orly understood. We report that TGF-beta receptor phosphorylation of S mad3 promotes its interaction with, the paralogous coactivators CEP an d p300, whereas CBP/p300 binding to non-phosphorylated ted Smad3 or it s' oligomerization partner Smad4 is negatively regulated by Smad-intra molecular interactions. Furthermore, p300 and TGP-beta receptor-phosph orylated Smad3 synergistically augment transcriptional activation. Thu s, CBP/p300 are important components of activin/TGF-beta signaling and may mediate the antioncogenic functions of Smad2 and Smad4.