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. 2017 Feb 25;8(20):33972–33989. doi: 10.18632/oncotarget.15687

Figure 2. Ubiquitination of β-catenin and its degradation.

Figure 2

The degradation of β-catenin mainly undergoes through Ubiquitin Proteosome System (UPS). Different ubiquitin E3 ligases in the cytoplasm and nucleus regulate the ubiquitination of β-catenin. Ubiquitination of β-catenin can be occurred either in the Wnt-off state or in the Wnt-on state. Together with Cul1 and Skp1, β-TrCP mediates the ubiquitination of β-catenin in the Wnt-off state. While Jade1, c-Cbl and Trim33 induce ubiquitination of β-catenin in the Wnt-on state. Additionally, SIAH1 along with SIP and Ebi, ubiquitinate β-catenin in response to p53 activition. Phosphrylation state is not always a necessary condition for β-catenin ubiquitination. β-TrCP and Trim33-induced ubiquitination of β-catenin is phosphorylation dependent, while ubiquitination of β-catenin by Jade-1, c-Cbl and SIAH1 are phosphorylation independent. In contrast to afore mentioned E3 ligases, EDD ubiquitinates β-catenin with an inhibitory effects on its degradation. Several deubiquitinases such as USP4 and USP7 can deubiquitinate β-catenin and interrupt its degradation process.