This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shimizu, K.
Right arrow Articles by Gurdon, J. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shimizu, K.
Right arrow Articles by Gurdon, J. B.

 Previous Article  |  Next Article 

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.


This article has been cited by other articles:

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


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»