Figure 3

Ubiquitination-mediated regulation of the core Wnt/β-catenin pathway components. Cell-surface transmembrane ubiquitin E3 ligases ZNRF3 and RNF43 target frizzled for lysosome degradation. UBPY deubiquitinates frizzled to recycle it to the plasma membrane. Palmitolylation and monoubiquitylation regulate LRP6 exit from the endoplasmic reticulum (ER). Multiple ubiquitin E3 ligases target Dvl for degradation, thus negatively regulate Wnt signaling. CYLD and USP14 are deubiquitinases responsible for removing K63-linked polyubiquitin chain of Dvl. RNF146 and Smurf2-mediated ubuiqitination targets Axin for degradation, whereas Smurf1-mediated ubuiqitination of Axin regulates its interaction with LRP5/6. USP15 protects APC from degradative ubuiqitnation. HectD1 modifies APC with K63-linked polyubiquitin chain to promote interaction between APC and Axin. Apart from the β-TrCP-mediated degradative ubiquitination of β-catenin, ubiquitination-mediated by ubiquitin-conjugating enzyme Rad6B increases β-catenin stability. Ubiquitin ligase Jade-1, which is primarily localized in the nucleus, may regulate abundance of the nucleus pool of β-catenin.