The study investigates the role of β-catenin in the ubiquitin-proteasome pathway and its regulation by the Wingless/Wnt signaling pathway. β-catenin, a central component of the cadherin cell adhesion complex, is tightly regulated in its steady-state level outside the cadherin-catenin complex. The authors show that the ubiquitin-dependent proteolysis system is involved in the regulation of β-catenin turnover. β-catenin, but not other cadherin-related proteins, becomes stabilized when proteasome-mediated proteolysis is inhibited, leading to the accumulation of multi-ubiquitinated forms of β-catenin. Mutagenesis experiments demonstrate that substitution of serine residues in the glycogen synthase kinase 3β (GSK3β) phosphorylation consensus motif of β-catenin inhibits ubiquitination and results in protein stabilization. This motif in β-catenin resembles a motif in 1xB (inhibitor of NFκB) required for the phosphorylation-dependent degradation of IκB via the ubiquitin-proteasome pathway. The study also shows that ubiquitination of β-catenin is reduced in Wnt-expressing cells, providing evidence that the ubiquitin-proteasome degradation pathway may act downstream of GSK3β in the regulation of β-catenin. These findings suggest a molecular link between the Wnt signaling pathway and the ubiquitin-proteasome degradation pathway, with GSK3β and the ubiquitination machinery using the same site in β-catenin.The study investigates the role of β-catenin in the ubiquitin-proteasome pathway and its regulation by the Wingless/Wnt signaling pathway. β-catenin, a central component of the cadherin cell adhesion complex, is tightly regulated in its steady-state level outside the cadherin-catenin complex. The authors show that the ubiquitin-dependent proteolysis system is involved in the regulation of β-catenin turnover. β-catenin, but not other cadherin-related proteins, becomes stabilized when proteasome-mediated proteolysis is inhibited, leading to the accumulation of multi-ubiquitinated forms of β-catenin. Mutagenesis experiments demonstrate that substitution of serine residues in the glycogen synthase kinase 3β (GSK3β) phosphorylation consensus motif of β-catenin inhibits ubiquitination and results in protein stabilization. This motif in β-catenin resembles a motif in 1xB (inhibitor of NFκB) required for the phosphorylation-dependent degradation of IκB via the ubiquitin-proteasome pathway. The study also shows that ubiquitination of β-catenin is reduced in Wnt-expressing cells, providing evidence that the ubiquitin-proteasome degradation pathway may act downstream of GSK3β in the regulation of β-catenin. These findings suggest a molecular link between the Wnt signaling pathway and the ubiquitin-proteasome degradation pathway, with GSK3β and the ubiquitination machinery using the same site in β-catenin.