Cyclin-dependent kinase 2 regulates the interaction of Axin with β-catenin

Axin, a negative regulator of Wnt, forms a complex with glycogen synthase kinase 3β, β-catenin, and adenomatous polyposis coli and promotes GSK3β-dependent phosphorylation of β-catenin, thereby stimulating degradation of the β-catenin. An essential step in that process is the phosphorylation of Axin. Examination of Axin's amino acid sequence revealed it to contain six arginine-X-leucine (RXL) sequences, the cyclin-dependent kinase 2 (CDK2) binding motif, and 10 CDK2 consensus phosphorylation sequences. We also found that cyclin A/CDK2 phosphorylates Axin, thereby enhancing its association with β-catenin. This suggests that cyclin A/CDK2 is a negative regulator of β-catenin-mediated signal transduction, which exerts its effects through phosphorylation of Axin.