β-catenin is a key component of the cadherin cell adhesion complex and plays a critical role in the Wnt signaling pathway. The study shows that β-catenin is regulated by the ubiquitin–proteasome pathway. When proteasome-mediated proteolysis is inhibited, β-catenin becomes stabilized, leading to the accumulation of multi-ubiquitinated forms. Mutagenesis experiments indicate that substitution of serine residues in the GSK3β phosphorylation consensus motif of β-catenin inhibits ubiquitination and stabilizes the protein. This motif in β-catenin is similar to that in IκB, which is required for phosphorylation-dependent degradation via the ubiquitin–proteasome pathway. The study provides the first evidence that the ubiquitin–proteasome degradation pathway may act downstream of GSK3β in the regulation of β-catenin. β-catenin is degraded by the proteasome pathway, and proteasome inhibitors like ALLN and lactacystin lead to the accumulation of higher molecular weight forms of β-catenin. These modifications are not due to hyperphosphorylation but rather to ubiquitination. The results show that β-catenin is ubiquitinated and that this process is reduced in Wnt-expressing cells. The GSK3β consensus phosphorylation site in β-catenin is necessary for ubiquitination, and mutations in this site prevent ubiquitination. The study also shows that Wnt-1 expression reduces the ubiquitination of β-catenin and increases its cytoplasmic stabilization. The findings suggest that the ubiquitin–proteasome pathway and the Wnt signaling pathway share a common site in β-catenin for regulation. The study provides evidence of a molecular link between the Wnt signaling pathway and the ubiquitin–proteasome degradation pathway. β-catenin is ubiquitinated, and this process is regulated by the GSK3β phosphorylation site. The results indicate that the ubiquitin–proteasome pathway is involved in the regulation of β-catenin turnover. The study demonstrates that β-catenin is regulated by the ubiquitin–proteasome pathway and that this pathway acts downstream of GSK3β in the regulation of β-catenin. The findings suggest that the ubiquitin–proteasome pathway is a key mechanism for the regulation of β-catenin levels.β-catenin is a key component of the cadherin cell adhesion complex and plays a critical role in the Wnt signaling pathway. The study shows that β-catenin is regulated by the ubiquitin–proteasome pathway. When proteasome-mediated proteolysis is inhibited, β-catenin becomes stabilized, leading to the accumulation of multi-ubiquitinated forms. Mutagenesis experiments indicate that substitution of serine residues in the GSK3β phosphorylation consensus motif of β-catenin inhibits ubiquitination and stabilizes the protein. This motif in β-catenin is similar to that in IκB, which is required for phosphorylation-dependent degradation via the ubiquitin–proteasome pathway. The study provides the first evidence that the ubiquitin–proteasome degradation pathway may act downstream of GSK3β in the regulation of β-catenin. β-catenin is degraded by the proteasome pathway, and proteasome inhibitors like ALLN and lactacystin lead to the accumulation of higher molecular weight forms of β-catenin. These modifications are not due to hyperphosphorylation but rather to ubiquitination. The results show that β-catenin is ubiquitinated and that this process is reduced in Wnt-expressing cells. The GSK3β consensus phosphorylation site in β-catenin is necessary for ubiquitination, and mutations in this site prevent ubiquitination. The study also shows that Wnt-1 expression reduces the ubiquitination of β-catenin and increases its cytoplasmic stabilization. The findings suggest that the ubiquitin–proteasome pathway and the Wnt signaling pathway share a common site in β-catenin for regulation. The study provides evidence of a molecular link between the Wnt signaling pathway and the ubiquitin–proteasome degradation pathway. β-catenin is ubiquitinated, and this process is regulated by the GSK3β phosphorylation site. The results indicate that the ubiquitin–proteasome pathway is involved in the regulation of β-catenin turnover. The study demonstrates that β-catenin is regulated by the ubiquitin–proteasome pathway and that this pathway acts downstream of GSK3β in the regulation of β-catenin. The findings suggest that the ubiquitin–proteasome pathway is a key mechanism for the regulation of β-catenin levels.