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XB-ART-12972
Proc Natl Acad Sci U S A. May 25, 1999; 96 (11): 6273-8.

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: R01GM 57603 NIGMS NIH HHS

Genes referenced: btrc gys1 skp1
Antibodies referenced:
Morpholinos referenced:

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