Table 1.
Various PTMs of PD-L1.
| Related enzymes | Modification site | Biological effects | Cancer type | Molecules | References | |
|---|---|---|---|---|---|---|
| N-glycosylation | GLT1D1 | N35 /N192 /N200 /N219 |
Enhanced stability of PD-L1 | Non-Hodgkin’s | (29) | |
| STT3 | N35 /N192 /N200 /N219 |
Enhanced stability of PD-L1 | Liver cell carcinoma | IL- 6 | (30) | |
| Colon cancer | (31, 32) | |||||
| Nasopharyngeal Carcinoma | TGF-β | (33) | ||||
| GFAT1 | N35 /N192 /N200 /N219 |
Enhanced stability of PD-L1 | Lung cancer | (34) | ||
| Glyco-PD-L1-processing enzymes | Reduced stability of PD- L1; Blocking PD-L1 from binding to PD- 1 binding | Breast cancer | (36) | |||
| 2-DG | Blocking PD-L1 from binding to PD- 1 binding | Triple negative breast cancer | (37–40) | |||
| B3GNT3 | N192 /N200 |
Promoting PD-L1 binding to PD-1 | EGF | (25) | ||
| Sigma1 | Enhanced stability of PD-L1 | Prostate Cancer/Triple negative breast cancer | (41) | |||
| FKBP51s | Enhanced stability of PD-L1 | Glioma | GSK3β,b-TrCP | (42) | ||
| STAT3 | Suppresses glycosylation of PD- L1, Activates the NF-kB/STAT3 and NF-kB | Pancreatic cancer | (43–46) | |||
| Ubiquitination | β-TrCP | K48 | Catalytic degradation of PD-L1 | Breast cancer | GSK3β, mTORC1/ p70S6K |
(56, 57) |
| SPOP | Decreases PD-L1 level | Prostate cancer | Cullin 3, D-CDK4/6 | (60, 61) | ||
| STUB1 | Downregulates level of PD-L1 | Melanoma | CMTM6 | (53, 62–64) | ||
| HRD1 | Downregulates level of PD-L1, Positively regulates T‐cell immunity | Breast cancer | ERAD, Metformin | (65) | ||
| DCU N1D1 |
Increases PD-L1 level | Colorectal cancer, Glioma, Prostate cancer and Lung cancer | FAK Pathway | (68, 69) | ||
| NEDD4 | K48 | Promotes PD-L1 degradation | Bladder caner | FGFR3 | (70) | |
| RNF 144A |
Promotes PD-L1 degradation | Bladder Tumor | EGFR | (71) | ||
| c-Cbl Cbl-b | Inhibition of PD-L1 expression | Melanoma, Gastric cancer, NSCLC | STAT5a, AKT, and ERK signaling pathways | (73, 74) | ||
| ARIH1 | Degradation of PD - L1 | Breast cancer | GSK3α | (76) | ||
| Deubiquitination | CSN5 | suppresses degradation of PD-L1 | Triple negative breast cancer, NSCLC | TNF-α, NF-κB signaling pathway |
(52, 84) | |
| USP22 | Enhanced stability of PD-L1 | Liver Cancer, NSCLC, PDA |
CSN5 | (86–88) | ||
| USP7 | Enhanced stability of PD-L1 | Lewis lung carcinoma | FOXP3 | (89) | ||
| USP9X | Enhanced stability of PD-L1 | OSCC, prostate cancer |
EGR | (94, 95, 128) | ||
| OTUD1 | K48 | Blocking PD-L1 degradation | Triple negative breast cancer | ERAD, circIGF2BP3 |
(97, 98) | |
| Phosphorylation | GSK3β | T180/S184; | Promotes β-TrCP-mediated PD-L1 degradation | Gastrointestinal tumors, Breast cancer, Lung cancer, Renal cell carcinoma, etc. | β-TrCP, EGF, EGFR |
(24, 99, 100, 104) |
| GSK3α | S279/S283 | Promotes ubiquitinated degradation of PD-L1 | Colon cancer, Cervical cancer, Pancreatic cancer, Lung cancer, Prostate cancer | ARIH1 | (24, 76) | |
| JAK1 | Y112 | (26, 76) | ||||
| AMPK | S195 | Aberrant glycosylation of PD-L1 upon degradation by ubiquitination | Breast cancer | ERAD, D-mannose |
(21, 105, 106) | |
| S283 | Induction of PD-L1 degradation | Breast cancer | metformin, CMTM4 |
(107) | ||
| NEK2 | T194/T210 | Glycosylation of PD-L1 to promote its stability | Liver Cancer | IL-6, OST, STT3A |
(111, 112) | |
| Acetylation | P300 | K263/K270 | Promotes PD-L1 internal transfer | Liver cell carcinoma | NF-κB, MHCI, HDAC2 |
(118, 119, 121) |
| HIP1R | Promotes PD-L1 internal transfer | AP2B1 | ||||
| S-palmitoylation | DHHC | C272 | Colon cancer, Breast cancer, Bladder cancer | Protects PD-L1 from degradation by lysosomes | (126, 127) | |