Fig. 1. The pathways of PD-L1 ubiquitination and degradation.

PD-L1 undergoes ubiquitination and degradation by E3 ubiquitin ligases, including STUB1, Cullin3^SPOP, and β-TrCP, which is abolished by CMTM4/6, CSN5, and STT3. Although glycosylation of PD-L1 increases its protein stability, the AMPK agonist or EGFR inhibitor reverses this process and induces PD-L1 proteasome-dependent degradation. Moreover, in response to extracellular stimuli, PD-L1 protein triggers ubiquitination and degradation by multiple pathways.