JCB logo
PeproTech: Your source for Cell Biology Research Reagents
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 29 July 2002. doi:10.1083/jcb.200203064
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hanai, J.-i.
Right arrow Articles by Sokol, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hanai, J.-i.
Right arrow Articles by Sokol, S.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525/2002/8/529 $5.00
The Journal of Cell Biology, Volume 158, Number 3, August 5, 2002 529-539

Article

 Endostatin is a potential inhibitor of Wnt signaling

Jun-ichi Hanai1, Joachim Gloy2,3, S. Ananth Karumanchi1, Sujata Kale1, Jian Tang1, Guang Hu1, Barden Chan1, Ramani Ramchandran1, Vivek Jha1, Vikas P. Sukhatme1 and Sergei Sokol2,3

1 Department of Medicine and Center for Study of the Tumor Microenvironment, Divisions of Nephrology, Hematology-Oncology
2 Molecular Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215
3 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02215

Address correspondence to Vikas P. Sukhatme, 330 Brookline Ave., Dana 517, Beth Israel Deaconess Medical Center, Boston, MA 02215. Tel.: (617) 667-2105. Fax: (617) 667-7843. E-mail: vsukhatm{at}caregroup.harvard.edu

Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. To gain insight into ES-mediated signaling, we studied the effects of ES RNA on Xenopus embryogenesis and observed developmental abnormalities consistent with impaired Wnt signaling. ES RNA blocked the axis duplication induced by ß-catenin, partially suppressed Wnt-dependent transcription, and stimulated degradation of both wild-type and "stabilized" forms of ß-catenin, the latter suggesting that ES signaling does not involve glycogen synthase kinase 3. Moreover, ES uses a pathway independent of the Siah1 protein in targeting ß-catenin for proteasome-mediated degradation. ES failed to suppress the effects of T cell–specific factor (TCF)-VP16 (TVP), a constitutive downstream transcriptional activator that acts independently of ß-catenin. Importantly, these data were replicated in endothelial cells and also in the DLD-1 colon carcinoma cells with the mutated adenomatous polyposis coli protein. Finally, suppression of endothelial cell migration and inhibition of cell cycle by ES were reversed by TVP. Though high levels of ES were used in both the Xenopus and endothelial cell studies and the effects on ß-catenin signaling were modest, these data argue that at pharmacological concentrations ES may impinge on Wnt signaling and promote ß-catenin degradation.

Key Words: endostatin; ß-catenin; migration; angiogenesis; Xenopus


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

A new path for endostatin
Alan W. Dove
J. Cell Biol. 2002 158: 383. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents