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SPOP functions as an adaptor to link the E3 ubiquitin ligase Cullin3 with the substrate PD-L1, which is required for PD-L1 ubiquitination and degradation. By interacting with Cullin3, SNX6 competes with SPOP for binding with Cullin3. Thus, SNX6 decreases SPOP interaction with Cullin3, which blocks PD-L1 ubiquitination and protects PD-L1 from being degraded. The change of PD-L1 levels on tumor cells regulates tumor-T-cell response.
