Shimizu et al. sought to identify proteins that interact with Smad2, a protein involved in activin and transforming growth factor-β (TGF-β)-dependent signaling. They identified Swift (Smad wing for transcriptional activation), a protein containing six BRCA1 COOH-terminal (BRCT) domains. Heterologously expressed Xenopus Swift localized to the nucleus in human cells. Swift bound to Smad2 in vitro and in vivo, and the association of these two proteins required the three BRCT domains located nearest the Swift COOH-terminus. Microinjection of Swift mRNA and an mRNA for constitutively activated activin receptor (ActRIB*) into Xenopus embryos led to synergistic gene expression compared to expression of ActRIB* alone. Injection of Smad2 and Swift mRNAs into Xenopus embryos gave results similar to those of Swift and ActRIB* mRNA injection. Overexpression of dominant-negative mutants of Swift in Xenopus embryos blocked ActRIB* signaling and led to deformed trunk development. The authors demonstrated that Swift has intrinsic transactivation activity, and further experiments indicated that Swift functions in TGF-β/activin but not in bone morphogenic protein (BMP) or in fibroblast growth factor (FGF) signaling. Thus, Swift appears to be a necessary component in activin signaling and Xenopus development and may signify the existence of a new family of transcriptional regulators.
K. Shimizu, P.-Y. Bourillot, S. J. Nielsen, A. M. Zorn, J. B. Gurdon, Swift is a novel BRCT domain coactivator of Smad2 in transforming growth factor-β signaling. Mol. Cell. Biol. 21, 3901-3912 (2001). [Abstract] [Full Text]