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

The EMBO journal | Jul 1, 1997

http://www.ncbi.nlm.nih.gov/pubmed/9233789

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 RIS Download

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