Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
J Cell Biol 2002 Aug 05;1583:529-39. doi: 10.1083/jcb.200203064.
Show Gene links Show Anatomy links

Endostatin is a potential inhibitor of Wnt signaling.

Hanai J , Gloy J , Karumanchi SA , Kale S , Tang J , Hu G , Chan B , Ramchandran R , Jha V , Sukhatme VP , Sokol S .

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 beta-catenin, partially suppressed Wnt-dependent transcription, and stimulated degradation of both wild-type and "stabilized" forms of beta-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 beta-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 beta-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 beta-catenin signaling were modest, these data argue that at pharmacological concentrations ES may impinge on Wnt signaling and promote beta-catenin degradation.

PubMed ID: 12147676
PMC ID: PMC2173844
Article link: J Cell Biol

Species referenced: Xenopus laevis
Genes referenced: acvr1 cat.2 ctnnb1 dld dvl1 dvl2 fgf2 gpc1 myc sia1 siah1 vegfa

Article Images: [+] show captions
References [+] :
Ackley, The NC1/endostatin domain of Caenorhabditis elegans type XVIII collagen affects cell migration and axon guidance. 2001, Pubmed