Table I.
Some E3 ligases involved in the crosstalk between tumors and the TME.
| Biological process | E3 ligase | Target | Category | Cancer/cell type | (Refs.) |
|---|---|---|---|---|---|
| Hypoxia | VHL | HIF-α | Tumor suppressor | (31) | |
| SIAH2 | NRF1 | Oncogene | Breast cancer | (36) | |
| Angiogenesis | MDM2 | HIF-α | Tumor suppressor | (39) | |
| SAG | Oncogene | B16F10 melanoma | (42,110) | ||
| FBW7 | Notch4 | Oncogene | (45) | ||
| c-CBL | β-catenin | Tumor suppressor | (48) | ||
| TRIM25 | SP1 | Tumor suppressor | Gastric cancer | (52) | |
| Chronic inflammation-mediated tumor formation | SCF-Skp2 | FOXO1 | Oncogene | Hepatoma, prostate cancer, lymphoma | (58) |
| MDM2 | FOXOs | Oncogene | (59) | ||
| SCF-Skp2 | E2F1 | HepG2 cells | (65) | ||
| LUBAC | NEMO | Oncogene | B-cell leukemia, breast cancer | (71,72) | |
| CAF | SCF-Fbxw7 | Notch1 | Tumor suppressor | BMSCs, melanoma cells | (90) |
| RNF5 | PTEN | Oncogene | Pancreatic ductal adenocarcinoma cells | (84) | |
| ECM | SCF-Skp2 | SP1 | Oncogene | Oral squamous cell carcinoma, lung cancer cells | (96,97) |
| NEDD4-1 | MT1-MMP | Oncogene | breast cancer cell MCF-7 | (103) | |
| TAM polarization | TRIM24 | CBP | Tumor suppressor | Macrophages | (105) |
| UBR5 | Oncogene | Ovarian cancer | (111) | ||
| T-cell immunosuppression | CRL4WDR4 | PML | Oncogene | Lung cancer | (117) |
| FBXO38 | PD-1 | Tumor suppressor | Colorectal carcinoma, hepatocellular carcinoma | (118) | |
| Cullin 3-SPOP | PD-L1 | Tumor suppressor | Prostate cancer, kidney cancer | (120,121) | |
| NEDD4 | GITR | Oncogene | Melanoma | (132) | |
| MDSC immunosuppression | TRAF6 | STAT3 | Tumor suppressor | Lung cancer | (134) |
| MDSC differentiation | TRIM29 | STING | Oncogene | Nasopharyngeal carcinoma | (137) |
| Myofibroblastic activation | SMURF1 | TGF-βRII | Tumor suppressor | Hepatic stellate cells | (164) |
| Antigen presentation | TRIM71 | Rb, p53 | Oncogene | Breast cancer | (141) |
| NK cell activation | Cbl-b | Tyro3, Mer, Axl | Oncogene | Melanoma, breast cancer | (143) |
| NK cell function | TRIM29 | TAB2 | Oncogene | NK cells | (146) |
CAFs, cancer-associated fibroblasts; Cbl-b, Casitas B-lineage lymphoma proto-oncogene-b; CBP, CREB-binding protein; CRL4WDR4, WD repeat 4-containing CUL-RING ubiquitin ligase 4; cullin 3-SPOP, cullin 3-speckle-type pox virus and zinc finger protein; ECM, extracellular matrix; E2F, E2 promoter binding factor; FBW7, F-box and WD repeat domain-containing 7; FOXO, Forkhead box O; GITR, glucocorticoid induced TNF receptor; LUBAC, a linear ubiquitin chain assembly complex; MDM2, mouse double minute 2 homolog; MDSCs, myeloid-derived suppressor cells; MT1-MMP, membrane type 1-matrix metalloproteinase; NEMO, nuclear factor-κB essential modulator; NK, natural killer; PD-1, programmed cell death protein-1; PD-L1, programmed cell death-ligand 1; PML, promyelocytic leukemia; RNF5, ring finger protein 5; SAG, sensitive to apoptosis gene; SIAH2, Siah E3 ubiquitin protein ligase 2; SCF, Skp-Cul1-F-box; Skp2, S-phase kinase-associated protein-2; SMURF1, SMAD Specific E3 ubiquitin protein ligase 1; TRIM, tripartite motif containing; TAB2, TGF-β activated kinase 1 binding protein 2; TAMs, tumor-associated macrophages; TGF-βRI, TGF-β type I receptor; TGF-βRII, TGF-β type II receptor; UBR5, ubiquitin protein ligase E3 component n-recognin 5; VHL, von Hippel Lindau.