| + |
B3GNT3 | up-regulates activity 
glycosylation
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275389 |
Asn192 |
KREEKLFNVTSTLRI |
Homo sapiens |
BT-549 Cell |
| pmid |
sentence |
| 29438695 |
These results further suggested that B3GNT3 mediates PD-L1 and PD-1 interaction through N-linked glycosylation instead of O-linked glycosylation |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-275390 |
Asn200 |
VTSTLRINTTTNEIF |
Homo sapiens |
BT-549 Cell |
| pmid |
sentence |
| 29438695 |
These results further suggested that B3GNT3 mediates PD-L1 and PD-1 interaction through N-linked glycosylation instead of O-linked glycosylation |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
GSK3B | down-regulates quantity by destabilization 
phosphorylation
|
CD274 |
0.3 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277275 |
Ser184 |
GKTTTTNsKREEKLF |
Homo sapiens |
BT-549 Cell |
| pmid |
sentence |
| 27572267 |
We show that glycogen synthase kinase 3β (GSK3β) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by β-TrCP. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277276 |
Thr180 |
QVLSGKTtTTNSKRE |
Homo sapiens |
BT-549 Cell |
| pmid |
sentence |
| 27572267 |
We show that glycogen synthase kinase 3β (GSK3β) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by β-TrCP. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
GSK3A | down-regulates quantity by destabilization
phosphorylation
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277552 |
Ser279 |
CGIQDTNsKKQSDTH |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 33879767 |
We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
NEK2 | up-regulates quantity by stabilization
phosphorylation
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277315 |
Thr194 |
EEKLFNVtSTLRINT |
Mus musculus |
Pancreatic Cancer Cell |
| pmid |
sentence |
| 34315872 |
NEK2 interacts with PD-L1, phosphorylating the T194/T210 residues and preventing ubiquitin-proteasome pathway-mediated degradation of PD-L1 in ER lumen. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277314 |
Thr210 |
TNEIFYCtFRRLDPE |
Mus musculus |
Pancreatic Cancer Cell |
| pmid |
sentence |
| 34315872 |
NEK2 interacts with PD-L1, phosphorylating the T194/T210 residues and preventing ubiquitin-proteasome pathway-mediated degradation of PD-L1 in ER lumen. |
|
| Publications: |
2 |
Organism: |
Mus Musculus |
| + |
FOXP3 | up-regulates quantity by expression
transcriptional regulation
|
CD274 |
0.463 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277728 |
|
|
Homo sapiens |
Pancreatic Cancer Cell |
| pmid |
sentence |
| 38339310 |
FOXP3 expression additionally increased programmed death ligand 1 (PD-L1) expression, which, when inhibited with CCL5, decreased the tumor burden and Treg infiltration in orthotopic murine, Pan-02 PDAC tumors |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
STT3A | up-regulates quantity by stabilization
glycosylation
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-274975 |
|
|
Homo sapiens |
MCF-10A Cell |
| pmid |
sentence |
| 29765039 |
Together, these results support a notion that the two STT3 isoforms regulate EMT-mediated PD-L1 induction through PD-L1 protein N-glycosylation and stabilization. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
COPS5 | up-regulates quantity by stabilization
deubiquitination
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-274977 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 27866850 |
The results suggested that TNF-α upregulates expression of CSN5, which interacts and deubiquitinates PD-L1 for protein stabilization. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SIGMAR1 | up-regulates quantity by stabilization
stabilization
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-274974 |
|
|
Homo sapiens |
MDA-MB-231 Cell |
| pmid |
sentence |
| 29117944 |
We propose that Sigma1 is a ligand-operated scaffolding protein that promotes the stability, processing, assembly, and trafficking of specific proteins in the secretory pathway of cancer cells. In support of this hypothesis, we found that siRNA-mediated knockdown of Sigma1 resulted in a significant decrease in PD-L1 protein levels in triple-negative MDA-MB-231 breast cancer and androgen-independent PC3 prostate cancer cells |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
HIF1A | up-regulates quantity by expression 
transcriptional regulation
|
CD274 |
0.279 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259092 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27141364 |
STAT3 and HIF-1α cooperatively enhance PD-L1 expression in EML4-ALK-translocated pADC cells under hypoxia. Taken together, these findings suggest that EML4-ALK might increase HIF-1α expression under hypoxia by enhancing transcription and inhibiting ubiquitination of HIF-1α, resulting in the stabilization of HIF-1α, consequently contributing to HIF-1α-mediated upregulation of PD-L1 under hypoxia. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GSK3B | down-regulates quantity
phosphorylation
|
CD274 |
0.3 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-279047 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27572267 |
Together, the results suggest that GSK3\u03b2 binds and phosphorylates the non-glycosylated PD-L1.|We show that glycogen synthase kinase 3\u03b2 (GSK3\u03b2) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by \u03b2-TrCP. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ITCH | down-regulates quantity by destabilization
ubiquitination
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278815 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 35638972 |
ITCH Ubiquitinates and Down-Regulates Tumor-Surface PD-L1.|The current study supports a model (Fig. 7) in which the E3 ligase ITCH mediates poly-ubiquitination of PD-L1 and down-regulates tumor cell-surface PD-L1 levels (via ubiquitin-directed lysosomal degradation) in MAPKi-adapted melanoma cells and in potentially other biologic contexts such quasi-mesenchymal tumor cell-states that contribute to therapy resistance and metastatic potential. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
STUB1 | down-regulates quantity by destabilization
destabilization
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-274979 |
|
|
Homo sapiens |
A-375 Cell |
| pmid |
sentence |
| 28813410 |
Deletion of STUB1 resulted in a more profound increase in PD-L1 levels in CMTM6 deficient than in CMTM6 proficient cells, identifying STUB1 as an E3 ligase that causes destabilization of PD-L1 (Fig. 4f,g), either by direct modification of one of the lysines in the PD-L1 cytoplasmic domain or indirectly |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CMTM4 | up-regulates quantity by stabilization
stabilization
|
CD274 |
0.346 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-274981 |
|
|
Homo sapiens |
A-375 Cell |
| pmid |
sentence |
| 28813410 |
Furthermore, the observations that (i) CMTM6 affects PD-L1 protein stability at late time points after biosynthesis; (ii) CMTM6, CMTM4 and PD-L1 interact, as shown by co-immunoprecipitation; and that (iii) CMTM6 is largely located at the cell surface, collectively suggest a model in which CMTM6 interacts with PD-L1 at the tumour cell surface and thereby protects it from degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CD274 | up-regulates
binding
|
PDCD1 |
0.939 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-82604 |
|
|
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 11015443 |
Pd-l1, was found to bind pd-1 specifically. The functional significance of this interaction has been demonstrated in t cell assays, in which engagement of pd-1 by pd-l1 leads to the inhibition of tcr-mediated lymphocyte proliferation and cytokine secretion. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KMT2C | up-regulates quantity by expression
transcriptional regulation
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260040 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 30385408 |
MLL3 enhances the transcription of PD-L1 and regulates anti-tumor immunity. We found that MLL3 bound to the enhancer of PD-L1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
FKBP5 | up-regulates quantity by expression
catalytic activity
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-274973 |
|
|
Homo sapiens |
U-251MG Cell |
| pmid |
sentence |
| 28978117 |
FKBP51s upregulated PD-L1 expression on the plasma membrane by catalysing the protein folding required for subsequent glycosylation. Inhibition of FKBP51s isomerase activity by SAFit decreased PD-L1 levels |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ARIH1 | down-regulates quantity by destabilization
ubiquitination, polyubiquitination
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-278582 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 33879767 |
E3 ubiquitin ligase ARIH1 directly ubiquitinates PD-L1 and targets it for proteasomal degradation, following EGFR inhibition. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277553 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 33879767 |
We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
STAT3 | up-regulates quantity by expression
transcriptional regulation
|
CD274 |
0.459 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259188 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27141364 |
STAT3 and HIF-1α cooperatively enhance PD-L1 expression in EML4-ALK-translocated pADC cells under hypoxia.The protein-DNA binding assay revealed that pSTAT3 was bound to the PD-L1 promoter region in H23 cells transfected with EML4-ALK. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SCF-betaTRCP | down-regulates quantity by destabilization
polyubiquitination
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277277 |
|
|
Homo sapiens |
BT-549 Cell |
| pmid |
sentence |
| 27572267 |
We show that glycogen synthase kinase 3β (GSK3β) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by β-TrCP. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
STT3B | up-regulates quantity by stabilization
glycosylation
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-274976 |
|
|
Homo sapiens |
MCF-10A Cell |
| pmid |
sentence |
| 29765039 |
Together, these results support a notion that the two STT3 isoforms regulate EMT-mediated PD-L1 induction through PD-L1 protein N-glycosylation and stabilization. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
YBX1 | up-regulates quantity by expression
transcriptional regulation
|
CD274 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282632 |
|
|
Homo sapiens |
PANC-1 Cell |
| pmid |
sentence |
| 40083936 |
TMBIM1 was significantly upregulated in pancreatic cancer tissues and cell lines, driving pancreatic cancer cell proliferation, growth, and migration both in vitro and in vivo. Elevated TMBIM1 expression induced high infiltration of MDSCs and fostered an immunosuppressive tumor microenvironment. Mechanistically, TMBIM1 binds to the transcription factor Y box binding protein 1 (YBX1), which in turn increases the affinity of YBX1 for the PD-L1 and CCL2 gene promoters. This interaction results in their upregulation, leading to increased MDSC infiltration, thereby facilitating the immunosuppressive TIME in PDAC. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CMTM6 | up-regulates quantity by stabilization
stabilization
|
CD274 |
0.462 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-274980 |
|
|
Homo sapiens |
A-375 Cell |
| pmid |
sentence |
| 28813410 |
Furthermore, the observations that (i) CMTM6 affects PD-L1 protein stability at late time points after biosynthesis; (ii) CMTM6, CMTM4 and PD-L1 interact, as shown by co-immunoprecipitation; and that (iii) CMTM6 is largely located at the cell surface, collectively suggest a model in which CMTM6 interacts with PD-L1 at the tumour cell surface and thereby protects it from degradation |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
SPOP | down-regulates quantity
ubiquitination
|
CD274 |
0.323 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-274978 |
|
|
Homo sapiens |
LNCaP-C4-2 Cell |
| pmid |
sentence |
| 29160310 |
Loss-of-function mutations in SPOP compromise ubiquitination-mediated PD-L1 degradation, leading to increased PD-L1 levels and reduced numbers of tumor-infiltrating lymphocytes (TILs) in mouse tumors and in primary human prostate cancer specimens. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
4.0
CD274
- 
- 