Fig. 2

Regulatory pathways governing PD-L1 via phosphorylation and ubiquitination. a In combination with JAK1, GSK3β, AMPK, EGF, STT3A, and IL-6 collaboratively facilitate serine/threonine phosphorylation of PD-L1, leading to subsequent ubiquitination. b β-TrCP, C-Cbl, Cbl-b, and DHA contribute to the increase in PD-L1 ubiquitination. Conversely, IFIT1 impedes PD-L1 ubiquitination. CDK4/6 enhances PD-L1 ubiquitination via SPOP. The E3 ubiquitin ligase HUWE1, in conjunction with PD-L1, facilitates PD-L1 ubiquitination. STUB1 stimulates PD-L1 ubiquitination, leading to subsequent degradation, while CMTM6/4 impedes the binding of PD-L1 to STUB1, thereby downregulating PD-L1 ubiquitination. Casp8 promotes PD-L1 ubiquitination by upregulating TNFAIP3. USP2 modulates the stability of VPRBP and facilitates PD-L1 ubiquitination. MIB2 catalyzes PD-L1 ubiquitination, mediating the trafficking of PD-L1 from the trans-Golgi network to the membrane through RAB8. Circular RNA-0000512 promotes PD-L1 ubiquitination by suppressing CMTM6 expression, while circular RNA-0067842 inhibits PD-L1 ubiquitination by upregulating CMTM6. The black arrows indicate positive regulation, and the red arrows indicate negative regulation