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β‐catenin is a target for the ubiquitin–proteasome pathway
Author(s) -
Aberle Hermann,
Bauer Andreas,
Stappert Jörg,
Kispert Andreas,
Kemler Rolf
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.13.3797
Subject(s) - biology , ubiquitin , proteasome , catenin , deubiquitinating enzyme , microbiology and biotechnology , beta catenin , genetics , signal transduction , computational biology , wnt signaling pathway , gene
β‐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 β‐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 β‐catenin turnover. β‐catenin, but not E‐cadherin, p120 cas or α‐catenin, becomes stabilized when proteasome‐mediated proteolysis is inhibited and this leads to the accumulation of multi‐ubiquitinated forms of β‐catenin. Mutagenesis experiments demonstrate that substitution of the serine residues in the glycogen synthase kinase 3β (GSK3β) phosphorylation consensus motif of β‐catenin inhibits ubiquitination and results in stabilization of the protein. This motif in β‐catenin resembles a motif in IκB (inhibitor of NFκB) which is required for the phosphorylation‐dependent degradation of IκB via the ubiquitin–proteasome pathway. We show that ubiquitination of β‐catenin is greatly reduced in Wnt‐expressing cells, providing the first evidence that the ubiquitin–proteasome degradation pathway may act downstream of GSK3β in the regulation of β‐catenin.

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