FIG. 4.

Regulation of β-catenin by the Cul1–Skp1–E3 ligase complex. In the absence of Wnt signaling, β-catenin forms a complex with GSK3β, casein kinase 1α (CK1α), Axin, and adenomatous polyposis coli (APC), resulting in CK1α-mediated phosphorylation of β-catenin (S45), followed by GSK3β-mediated phosphorylation of β-catenin at additional residues (T41, S37, S33). Phosphorylation of β-catenin allows it to be recognized by βTrCP1 and targeted for ubiquitination by the Cul1–Skp1–E3 ligase and subsequent degradation by the 26S proteasome.