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.
XB-ART-12972
Proc Natl Acad Sci U S A 1999 May 25;9611:6273-8. doi: 10.1073/pnas.96.11.6273.
Show Gene links Show Anatomy links

beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation.

Liu C , Kato Y , Zhang Z , Do VM , Yankner BA , He X .


Abstract
Regulation of beta-catenin stability is essential for Wnt signal transduction during development and tumorigenesis. It is well known that serine-phosphorylation of beta-catenin by the Axin-glycogen synthase kinase (GSK)-3beta complex targets beta-catenin for ubiquitination-degradation, and mutations at critical phosphoserine residues stabilize beta-catenin and cause human cancers. How beta-catenin phosphorylation results in its degradation is undefined. Here we show that phosphorylated beta-catenin is specifically recognized by beta-Trcp, an F-box/WD40-repeat protein that also associates with Skp1, an essential component of the ubiquitination apparatus. beta-catenin harboring mutations at the critical phosphoserine residues escapes recognition by beta-Trcp, thus providing a molecular explanation for why these mutations cause beta-catenin accumulation that leads to cancer. Inhibition of endogenous beta-Trcp function by a dominant negative mutant stabilizes beta-catenin, activates Wnt/beta-catenin signaling, and induces axis formation in Xenopus embryos. Therefore, beta-Trcp plays a central role in recruiting phosphorylated beta-catenin for degradation and in dorsoventral patterning of the Xenopus embryo.

PubMed ID: 10339577
PMC ID: PMC26871
Article link: Proc Natl Acad Sci U S A
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: axin1 btrc ctnnb1 gsc gsk3b gys1 myc nodal3.1 skp1


Article Images: [+] show captions
References [+] :
Aberle, beta-catenin is a target for the ubiquitin-proteasome pathway. 1997, Pubmed