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beta-catenin is a target for the ubiquitin-proteasome pathway.

beta-catenin is a central component of the cadherin cell adhesion complex and plays an essential role in the Wingless/Wnt signaling pathway. In the current model of this pathway, the amount of beta-catenin (or its invertebrate homolog Armadillo) is tightly regulated and its steady-state level outside the cadherin-catenin complex is low in the absence of Wingless/Wnt signal. Here we show that the ubiquitin-dependent proteolysis system is involved in the regulation of beta-catenin turnover. beta-catenin, but not E-cadherin, p120(cas) or alpha-catenin, becomes stabilized when proteasome-mediated proteolysis is inhibited and this leads to the accumulation of multi-ubiquitinated forms of beta-catenin. Mutagenesis experiments demonstrate that substitution of the serine residues in the glycogen synthase kinase 3beta (GSK3beta) phosphorylation consensus motif of beta-catenin inhibits ubiquitination and results in stabilization of the protein. This motif in beta-catenin resembles a motif in IkappaB (inhibitor of NFkappaB) which is required for the phosphorylation-dependent degradation of IkappaB via the ubiquitin-proteasome pathway. We show that ubiquitination of beta-catenin is greatly reduced in Wnt-expressing cells, providing the first evidence that the ubiquitin-proteasome degradation pathway may act downstream of GSK3beta in the regulation of beta-catenin.

Pubmed ID: 9233789

Authors

  • Aberle H
  • Bauer A
  • Stappert J
  • Kispert A
  • Kemler R

Journal

The EMBO journal

Publication Data

July 1, 1997

Associated Grants

None

Mesh Terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cadherins
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Line
  • Consensus Sequence
  • Cysteine Endopeptidases
  • Cytoskeletal Proteins
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • Humans
  • Mice
  • Molecular Sequence Data
  • Multienzyme Complexes
  • Phosphorylation
  • Proteasome Endopeptidase Complex
  • Signal Transduction
  • Trans-Activators
  • Tumor Cells, Cultured
  • Ubiquitins
  • beta Catenin