Swift Is a Novel BRCT Domain Coactivator of Smad2 in Transforming Growth Factor b Signaling

Transforming growth factor b (TGFb) signaling is transduced via Smad2–Smad4–DNA-binding protein complexes which bind to responsive elements in the promoters of target genes. However, the mechanism of how the complexes activate the target genes is unclear. Here we identify Xenopus Swift, a novel nuclear BRCT (BRCA1 C-terminal) domain protein that physically interacts with Smad2 via its BRCT domains. We examine the activity of Swift in relation to gene activation in Xenopus embryos. Swift mRNA has an expression pattern similar to that of Smad2. Swift has intrinsic transactivation activity and activates target gene transcription in a TGFb-Smad2-dependent manner. Inhibition of Swift activity results in the suppression of TGFb-induced gene transcription and defective mesendoderm development. Blocking Swift function affects neither bone morphogenic protein nor fibroblast growth factor signaling during early development. We conclude that Swift is a novel coactivator of Smad2 and that Swift has a critical role in embryonic TGFb-induced gene transcrip-tion. Our results suggest that Swift may be a general component of TGFb signaling. Transforming growth factor b (TGFb) superfamily signaling mediates a very diverse array of biological processes, including immune function, growth control, cell differentiation, pattern-ing the embryonic body, sexual reproduction, and skeletal for