HUMAN SMAD3 AND SMAD4 ARE SEQUENCE-SPECIFIC TRANSCRIPTION ACTIVATORS

Mounting evidence indicates that Smad proteins are required for TGF be ta signaling, but the way(s) in which Smad proteins propagate this sig nal is unclear. We found that two human Smad proteins (Smad3 and smad4 ) could specifically recognize an identical 8 bp palindromic sequence (GTCTAGAC). Tandem repeats of this palindrome conferred striking TGF b eta responsiveness to a minimal promoter. This responsiveness was abro gated by targeted deletion of the cellular Smad4 gene. These results d efine a novel biochemical property of Smad proteins that is likely to play a direct role in the biologic responses to TGF beta and related l igands.