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

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 acce...

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Veröffentlicht in:Molecular cell 2000-03, Vol.5 (3), p.523-532
Hauptverfasser: Salic, A, Lee, E, Mayer, L, Kirschner, M W
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creator Salic, A
Lee, E
Mayer, L
Kirschner, M W
description 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.
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subjects Adaptor Proteins, Signal Transducing
Adenomatous Polyposis Coli Protein
anaphase-promoting complex
Animals
axin
Axin Protein
beta -catenin
Calcium-Calmodulin-Dependent Protein Kinases - metabolism
Carrier Proteins - metabolism
Cell-Free System
Cytoplasm - metabolism
Cytoskeletal Proteins - metabolism
Dishevelled Proteins
Freshwater
GBP/Frat1 protein
Glycogen Synthase Kinase 3
Models, Biological
Ovum - metabolism
Phosphoproteins
Phosphorylation
Protein Binding
Protein Structure, Tertiary
Proteins - metabolism
Proto-Oncogene Proteins - metabolism
Repressor Proteins
Subcellular Fractions - metabolism
Trans-Activators
Ubiquitins - metabolism
Wnt protein
Wnt Proteins
Xenopus
Xenopus - embryology
Xenopus Proteins
Zebrafish Proteins
title Control of beta-catenin stability: reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts
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