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

Mol Cell. 2000 Mar;5(3):523-32. doi: 10.1016/s1097-2765(00)80446-3.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenomatous Polyposis Coli Protein
  • Animals
  • Axin Protein
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Carrier Proteins / metabolism
  • Cell-Free System
  • Cytoplasm / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • Dishevelled Proteins
  • Glycogen Synthase Kinase 3
  • Intracellular Signaling Peptides and Proteins
  • 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 Proteins
  • Xenopus / embryology*
  • Xenopus Proteins*
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • Adaptor Proteins, Signal Transducing
  • Adenomatous Polyposis Coli Protein
  • Axin Protein
  • CTNNB1 protein, Xenopus
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Dishevelled Proteins
  • Intracellular Signaling Peptides and Proteins
  • PIAS1 protein, Xenopus
  • Phosphoproteins
  • Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Trans-Activators
  • Ubiquitins
  • Wnt Proteins
  • Xenopus Proteins
  • Zebrafish Proteins
  • axin1 protein, Xenopus
  • beta Catenin
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3