Figure 2.

USP15 suppresses TNFα and Wnt signaling in association with CSN. Upon stimulation by TNFα, NF-ĸB is activated through phosphorylation and ubiquitin-dependent degradation of IĸB by CRL/SCF^βTrCP E3 ubiquitin ligase to turn on its downstream target genes. USP15, in association with CSN, deubiquitinates and promotes IĸB stabilization by inhibiting CRL/SCF^βTrCP activity and hinders NF-ĸB signaling (left) [33]. USP15 negatively regulates Wnt/β-catenin signaling by promoting the formation of the β-catenin destruction complex. In association with CSN, USP15 deubiquitinates and induces the stability of the essential component of the β-catenin destruction complex APC, which is required to target the phosphorylated β-catenin for CRLβ-TrCP-dependent proteasomal degradation (right) [35].