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Molecular and Cellular Biology, June 2001, p. 3901-3912, Vol. 21, No. 12
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.12.3901-3912.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Kazuya Shimizu,dagger Pierre-Yves Bourillot, Søren J. Nielsen, Aaron M. Zorn, and J. B. Gurdon*

Wellcome Trust Cancer Research Campaign Institute, Cambridge CB2 1QR, and Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, United Kingdom

Received 2 November 2000/Returned for modification 5 December 2000/Accepted 14 March 2001

Transforming growth factor beta  (TGFbeta ) 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 TGFbeta -Smad2-dependent manner. Inhibition of Swift activity results in the suppression of TGFbeta -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 TGFbeta -induced gene transcription. Our results suggest that Swift may be a general component of TGFbeta signaling.

* Corresponding author. Mailing address: Wellcome Trust Cancer Research Campaign Institute, Tennis Court Rd., Cambridge CB2 1QR, United Kingdom. Phone: 44-1223-334090. Fax: 44-1223-334185. E-mail: j.b.gurdon{at}welc.cam.ac.uk.

dagger Present address: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, 565-0871, Japan.

Molecular and Cellular Biology, June 2001, p. 3901-3912, Vol. 21, No. 12
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.12.3901-3912.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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