• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


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

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


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


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

May 25, 1999

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01GM 57603

Mesh Terms

  • Animals
  • Axin Protein
  • Body Patterning
  • Cadherins
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Embryo, Nonmammalian
  • GTP-Binding Proteins
  • Glycogen Synthase Kinase 3
  • Humans
  • Microtubule-Associated Proteins
  • Phosphorylation
  • Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Signal Transduction
  • Trans-Activators
  • Transcription, Genetic
  • Xenopus Proteins
  • Xenopus laevis
  • beta Catenin
  • beta-Transducin Repeat-Containing Proteins