Table 1.
The table summarizes various physiological roles of UPP and the enzymes/proteins involved in a cancer type.
| S. No. | Type of Enzyme | Enzymes Involved | Modulation of Pathways Involved |
Cancer Type | References |
|---|---|---|---|---|---|
| 1. | E3 ligase | Ectodermin, TRIM 47 | ↓ Smad 4 in TGF-β signaling | Promotes colorectal cancer | [75] |
| 2. | E3 ligase | FBXW7 | ↓ Wnt/β-catenin | Inhibits colorectal cancer | [71] |
| 3. | Deubiquitinating enzymes | USP5 | ↑ Wnt/β-catenin | Promotes colorectal cancer | [72] |
| 4. | Deubiquitinating enzymes | USP11, USP21 | ↑ERK/MAPK | Promotes colorectal cancer | [73,74] |
| 5. | Deubiquitinating enzymes | UBE2T | ↓ p53 pathway, ↑pentose phosphate pathway, etc., | Promotes colorectal cancer | [76] |
| 6. | E3 ligase | TRIM 67 | ↓ p53 degradation | Inhibits colorectal cancer | [75] |
| 7. | Ubiquitin-conjugating enzyme E2C | UBE2C | Pro-apoptotic | Inhibits esophageal cancer | [77] |
| 8. | E3 ligase | TRIM36 | ↑ Wnt/β-catenin | Promotes esophageal cancer | [78] |
| 9. | E3 ligase | TRIM44 | ↑ mTOR | Promotes esophageal cancer | [79] |
| 10. | E3 ligase | TRIM16 | ↑ TGF β/Snail | Promotes esophageal cancer | [80] |
| 11. | E3 ligase | RNF113A | ---- | Promotes esophageal cancer | [81] |
| 12. | E3 ligase | MARCH 8 | ---- | Promotes esophageal cancer | [82] |
| 13. | E3 ligase | Gankyrin | ↑ p53 degradation | Promotes esophageal cancer | [83] |
| 14. | Deubiquitinating enzymes | Ubiquitin carboxyl-terminal hydrolase 37 | ↑ TGF-β signaling | Promotes esophageal cancer | [84] |
| 15. | E2 ligase | Uev1A | bone morphogenetic protein signaling | Inhibits osteosarcoma | [85] |
| 16. | E3 ligase | Nedd4 | ↑ TGF-β signaling | Promotes osteosarcoma | [86] |
| 17. | E3 ligase | USP7 | ↑ Wnt/β-catenin | Promotes osteosarcoma | [87] |
| 18. | Deubiquitinating enzymes | USP1 | stabilize “inhibitors of DNA binding.” | Promotes osteosarcoma | [88] |
| 19. | E3 ligase | Deltex1 | ↓ NOTCH/HES1 | Inhibits osteosarcoma | [89] |
| 20. | E2 ligase | FAT10 | ↓ Hippo/YAP1 | Inhibits osteosarcoma | [90] |
| 21. | Deubiquitinating enzymes | USP39 | ↑ p21 | Inhibits osteosarcoma | [91] |
| 22. | E3 ligases | TRIM46, TRIM21, TRIM14, and TRIM23 | ↑NF-κB | Promotes osteosarcoma | [92] |
| 23. | E3 ligases | TRIM59 and TRIM7 | ↓ p53 and E-Cadherin | Promotes osteosarcoma | [93,94] |
| 24. | Deubiquitinating enzymes and E2 ligases | USP22 and UBE2T | ↑ PI3K/AKT | Promotes osteosarcoma | [95,96] |
| 25. | E3 ligases | Smurf1 | ↑ TGF-β signaling | Promotes lung cancer | [70] |
| 26. | E3 ligases | NEDD4-1 | ↑ PI3K/PTEN | Promotes lung cancer | [97] |
| 27. | E3 ligases | NEDD4 | EGFR mutation | Promotes lung cancer | [98] |
| 28. | E3 ligases | UBE3A | ↓ p16INK4a | Promotes lung cancer | [99] |
| 29. | E3 ligases | HRD1 | ↓ Sirtuin 2 | Promotes lung cancer | [100] |
| 30. | Deubiquitinating enzymes | USP37 | ↑ c-Myc | Promotes lung cancer | [101] |
| 31. | E3 ligases | TRIM7, TRIM71 | ↑ NF-κB | Promotes lung cancer | [102,103] |
| 32. | E2C ligases | UBE2C | ↑ ERK | Promotes Lung cancer | [104] |
| 33. | E3 ligases | UBE3C, TRIM59 | ↓ p53 | Promotes Lung cancer | [105,106] |
| 34. | Deubiquitinating enzymes | USP22 | ↑ ERK/AKT | Promotes lung cancer | [107] |
| 35. | E3 ligases | Prickle-1 | ↓ Wnt/β-catenin | Inhibits liver cancer | [108] |
| 36. | E3 ligases | TRIM31 | ↑ mTOR | Promotes liver cancer | [109] |
| 37. | E3 ligases | TRIM7 | ↓ PI3K | Inhibits liver cancer | [110] |
| 38. | E3 ligases | TRIM32 | ↑ mutated p53 | Promotes liver cancer | [111] |
| 39. | E3 ligases | TRIM65 | ↑ β-catenin | Promotes liver cancer | [112] |
| 40. | E2 ligases | UBE2L3 | ↓ p65 | Promotes liver cancer | [113] |
| 41. | E2 ligases | UBE2T | ↓ p53, p21, and noxa | Promotes liver cancer | [114] |
| 42. | Deubiquitinating enzymes | CYLD | ↓ NF-κB | Inhibits liver cancer | [115] |
| 43. | Deubiquitinating enzymes | UCHL1 | Apoptotic resistance | Promotes liver cancer | [116,117] |
| 44. | E3 ligases | NEDD4 | ↑ PTEN/PI3K/AKT | Promotes liver cancer | [118] |
| 45. | E3 ligases | FAT10 | ----- | Promotes liver cancer | [119] |
| 46. | E3 ligases | USP7 | Facilitates DNA repair by stabilizing MDC1 | Promotes cervical cancer | [120] |
| 47. | E2 ligases | E2-EPF | ↑ pVHL-HIF | Promotes cervical cancer | [121] |
| 48. | E3 ligases | MARCH 7 | ↑ VAV1/RAC1/CDC42 | Promotes cervical cancer | [122] |
| 49. | Deubiquitinating enzymes | Ovarian-tumor proteases deubiquitinase 5 | ↑ PI3K-AKT | Promotes cervical cancer | [123] |
| 50. | E3 ligases and E2 ligases | UHRF1, UBE2L6 | Promotes hypermethylation | Promotes cervical cancer | [124] |
| 51. | Deubiquitinating enzymes | USP18 | ↑ PI3K/AKT | Promotes cervical cancer | [125] |
| 52. | E3 ligases | UBE3A | ↓ ERK | Inhibits cervical cancer | [126] |
| 53. | Deubiquitinating enzymes | USP8 | Stabilizes FLIPL and EGFR signaling | Promotes cervical cancer | [127] |
| 54. | E3 ligases | TRIM 24 | ↑NF-κB/AKT | Promotes cervical cancer | [128] |
| 55. | E3 ligases | TRIM59 | ↓ p53 pathway, ↑ Ras/Rad, ↑ ERK | Promotes cervical cancer | [129] |
| 56. | E3 ligases | TRIM3 | ↑ p53 pathway, ↑ Caspase 3 | Inhibits cervical cancer | [130] |
| 57. | E1 ligases | UBA2 | ↑ ERK1/2, STAT3, and STAT5 | Promotes leukemia | [131] |
| 58. | E2 ligases and E2R1 | UBE2Q2 and CDC34 | ↓ IκB | Promotes leukemia | [132] |
| 59. | E2 ligases | UBE2E1 | ↓ HOX gene (HOXA9 and HOXA10) | Inhibits leukemia | [133] |
| 60. | E3 ligase | Fbxw7 | ↑ c-Myc, Notch1 | Promotes leukemia | [134] |
| 61. | E3 ligases | Triad1 | ↓HOX genes | Inhibits leukemia | [135] |
| 62. | E3 ligases | RNF20 | Interacts with histone H3 lys79 (H3K79) methyltransferase DOT1L | Promotes leukemia | [136] |
| 63. | E3 ligase | USP7 | ↑ NOTCH1 | Promotes leukemia | [137] |
| 64. | Deubiquitinating enzymes | USP22 | Stabilize BMI1 | Promotes leukemia | [138] |
| 65. | E3 ligases | TRIM62 | ↑ NOTCH and β-catenin signaling | Promotes leukemia | [139] |