Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Mol. Cell. Biol. 21 (12): 3901-3912

Copyright © 2001 by the American Society for Microbiology. All rights reserved.

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}

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.

Quantitative Dissection and Stoichiometry Determination of the Human SET1/MLL Histone Methyltransferase Complexes.
R. van Nuland, A. H. Smits, P. Pallaki, P. W. T. C. Jansen, M. Vermeulen, and H. T. M. Timmers (2013)
Mol. Cell. Biol. 33, 2067-2077
   Abstract »    Full Text »    PDF »
The regulation of TGF{beta} signal transduction.
A. Moustakas and C.-H. Heldin (2009)
Development 136, 3699-3714
   Abstract »    Full Text »    PDF »
Drosophila ptip is essential for anterior/posterior patterning in development and interacts with the PcG and trxG pathways.
M. Fang, H. Ren, J. Liu, K. M. Cadigan, S. R. Patel, and G. R. Dressler (2009)
Development 136, 1929-1938
   Abstract »    Full Text »    PDF »
Control of histone methylation and genome stability by PTIP.
I. M. Munoz and J. Rouse (2009)
EMBO Rep. 10, 239-245
   Abstract »    Full Text »    PDF »
An Allelic Series Uncovers Novel Roles of the BRCT Domain-Containing Protein PTIP in Mouse Embryonic Vascular Development.
W. Mu, W. Wang, and J. C. Schimenti (2008)
Mol. Cell. Biol. 28, 6439-6451
   Abstract »    Full Text »    PDF »
PTIP Associates with MLL3- and MLL4-containing Histone H3 Lysine 4 Methyltransferase Complex.
Y.-W. Cho, T. Hong, S. Hong, H. Guo, H. Yu, D. Kim, T. Guszczynski, G. R. Dressler, T. D. Copeland, M. Kalkum, et al. (2007)
J. Biol. Chem. 282, 20395-20406
   Abstract »    Full Text »    PDF »
Pax Transactivation-Domain Interacting Protein Is Required for Urine Concentration and Osmotolerance in Collecting Duct Epithelia.
D. Kim, M. Wang, Q. Cai, H. Brooks, and G. R. Dressler (2007)
J. Am. Soc. Nephrol. 18, 1458-1465
   Abstract »    Full Text »    PDF »
Knockdown of ALR (MLL2) Reveals ALR Target Genes and Leads to Alterations in Cell Adhesion and Growth.
I. Issaeva, Y. Zonis, T. Rozovskaia, K. Orlovsky, C. M. Croce, T. Nakamura, A. Mazo, L. Eisenbach, and E. Canaani (2007)
Mol. Cell. Biol. 27, 1889-1903
   Abstract »    Full Text »    PDF »
The pleiotropic roles of transforming growth factor beta in homeostasis and carcinogenesis of endocrine organs..
M. C Fleisch, C. A Maxwell, and M.-H. Barcellos-Hoff (2006)
Endocr. Relat. Cancer 13, 379-400
   Abstract »    Full Text »    PDF »
Smad transcription factors.
J. Massague, J. Seoane, and D. Wotton (2005)
Genes & Dev. 19, 2783-2810
   Abstract »    Full Text »    PDF »
Human PTIP Facilitates ATM-mediated Activation of p53 and Promotes Cellular Resistance to Ionizing Radiation.
P. A. Jowsey, A. J. Doherty, and J. Rouse (2004)
J. Biol. Chem. 279, 55562-55569
   Abstract »    Full Text »    PDF »
Negative regulation of Smad2 by PIASy is required for proper Xenopus mesoderm formation.
M. Daniels, K. Shimizu, A. M. Zorn, and S.-i. Ohnuma (2004)
Development 131, 5613-5626
   Abstract »    Full Text »    PDF »
BRCT Repeats As Phosphopeptide-Binding Modules Involved in Protein Targeting.
I. A. Manke, D. M. Lowery, A. Nguyen, and M. B. Yaffe (2003)
Science 302, 636-639
   Abstract »    Full Text »    PDF »
BRCT Domain-Containing Protein PTIP Is Essential for Progression through Mitosis.
E. A. Cho, M. J. Prindle, and G. R. Dressler (2003)
Mol. Cell. Biol. 23, 1666-1673
   Abstract »    Full Text »    PDF »
Extracellular Matrix Enhances Heregulin-Dependent BRCA1 Phosphorylation and Suppresses BRCA1 Expression through Its C Terminus.
T. Miralem and H. K. Avraham (2003)
Mol. Cell. Biol. 23, 579-593
   Abstract »    Full Text »    PDF »
A Functional Interaction between the Human Papillomavirus 16 Transcription/Replication Factor E2 and the DNA Damage Response Protein TopBP1.
W. Boner, E. R. Taylor, E. Tsirimonaki, K. Yamane, M. S. Campo, and I. M. Morgan (2002)
J. Biol. Chem. 277, 22297-22303
   Abstract »    Full Text »    PDF »
Smad regulation in TGF-{beta} signal transduction.
A. Moustakas, S. Souchelnytskyi, and C.-H. Heldin (2001)
J. Cell Sci. 114, 4359-4369
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882