Fig. 1

Regulation of non-histone acetylation on canonical Wnt/β-catenin signaling. Without the binding of Wnt molecules to the FZD-LRP5/6 co-receptor complex, the signaling is inactive (Wnt off state). During the Wnt off state, the destruction complex composed of GSK3β, APC, Axin1, and CK1, can interact with β-catenin, leading to its degradation with ubiquitin–proteasome in the cytoplasm. When Wnt molecules interact with the FZD-LRP5/6 co-receptor (Wnt on state), the complex recruits Axin and DVL to induce the release of β-catenin from the destruction complex and enhance its accumulation as well as nuclear translocation. In the cell nucleus, β-catenin interacts with LEF/TCF and further activates Wnt-dependent gene transcription. During the Wnt off state, acetylation of β-catenin can be inhibited by SIRT1, SIRT2, HDAC1, HDAC2, HDAC4, HDAC6, and HDAC67 to block its activity. During the Wnt on state, LRP6 is acetylated by p300 to facilitate signaling activation. Then, β-catenin is capable of being acetylated by CBP, p300, and PCAF to increase protein activity. Also, acetylation of GSK3β is suppressed by SIRT1, SIRT2, and SIRT3. TCF is acetylated by CBP