Control of beta-catenin stability: reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts.

Salic A, Lee E, Mayer L, Kirschner MW
Mol Cell. 2000 5 (3): 523-32

PMID: 10882137

Regulation of beta-catenin degradation by intracellular components of the wnt pathway was reconstituted in cytoplasmic extracts of Xenopus eggs and embryos. The ubiquitin-dependent beta-catenin degradation in extracts displays a biochemical requirement for axin, GSK3, and APC. Axin dramatically accelerates while dishevelled inhibits beta-catenin turnover. Through another domain, dishevelled recruits GBP/Frat1 to the APC-axin-GSK3 complex. Our results confirm and extend models in which inhibition of GSK3 has two synergistic effects: (1) reduction of APC phosphorylation and loss of affinity for beta-catenin and (2) reduction of beta-catenin phosphorylation and consequent loss of its affinity for the SCF ubiquitin ligase complex. Dishevelled thus stabilizes beta-catenin, which can dissociate from the APC/axin complex and participate in transcriptional activation.

MeSH Terms (28)

Adaptor Proteins, Signal Transducing Adenomatous Polyposis Coli Protein Animals Axin Protein beta Catenin Calcium-Calmodulin-Dependent Protein Kinases Carrier Proteins Cell-Free System Cytoplasm Cytoskeletal Proteins Dishevelled Proteins Glycogen Synthase Kinase 3 Models, Biological Ovum Phosphoproteins Phosphorylation Protein Binding Proteins Protein Structure, Tertiary Proto-Oncogene Proteins Repressor Proteins Subcellular Fractions Trans-Activators Ubiquitins Wnt Proteins Xenopus Xenopus Proteins Zebrafish Proteins

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