Regulation of Wnt/β-catenin and Hippo signaling pathways by SET7/9. SET7/9 can methylate YAP K494 and β-catenin K180. Under normal conditions, methylation of β-catenin by SET7/9 promotes GSK-3β-mediated ubiquitination and degradation of the protein. Upon Hippo signaling, methylation of YAP K494 by SET7/9 binds YAP in the cytoplasm, while upon Wnt signaling activation, methylation of YAP K494 by SET7/9 leads to dissociation of the YAP-AXIN-β-catenin complex, releases β-catenin and promotes its nuclear translocation, thus facilitates Wnt/β-catenin-dependent tumorigenesis.