The ubiquitin proteasome system (UPS) governs the non-lysosomal degradation of oxidized, damaged, or misfolded proteins in eukaryotic cells. This process is tightly regulated through the activation and transfer of polyubiquitin chains to target proteins which are then recognized and degraded by the 26S proteasome complex. The role of UPS is crucial in regulating protein levels through degradation to maintain fundamental cellular processes such as growth, division, signal transduction, and stress response. Dysregulation of the UPS, resulting in loss of ability to maintain protein quality through proteolysis, is closely related to the development of various malignancies and tumorigenesis.
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Family | Name | Role | Cancer Type | Function | Test Model | Reference |
---|---|---|---|---|---|---|
E2 | UBE2C | Oncogene | Gastric | Chromosomal stability, Proliferation, Migration, Invasion | In vitro, In vivo | [23] |
Oncogene | Colon | Cell cycle, Proloferation | In vitro | [24] | ||
Oncogene | Colorectal | Proliferation, Invasion | In vitro | [25] | ||
Oncogene | Thyroid | Proliferation | In vitro | [26] | ||
Oncogene | Breast | Proliferation, Drug resistance, Radiation resistance | In vitro | [27] | ||
Oncogene | Liver | Proliferation, Drug resistance, Migration, Invasion | In vitro | [28] | ||
Oncogene | Non-small cell lung | Drug resistance | In vitro | [29] | ||
UBE2Q1 | Oncogene | Colorectal | Proliferation | [30] | ||
Oncogene | Liver | p53 signaling, Cell cycle | In vitro | [31] | ||
Oncogene | Breast | p53 signaling | In vitro | [32] | ||
UBE2S | Oncogene | Endometrial | SOX6/β-catenin signaling, Proliferation | In vitro | [33] | |
Oncogene | Lung adenocarcinoma | Proliferation, p53 signaling, Apoptosis | In vitro | [34] | ||
Oncogene | Liver | p53 signaling, Cell cycle | In vitro | [35] | ||
E3 | FBW7 | Tumor suppressor | Burkitt’s lymphoma | c-Myc signaling | In vitro | [36][37] |
Tumor suppressor | Chronic myelogenous leukemia | c-Myc signaling | In vitro, In vivo | [38] | ||
Lipogenesis | Lung, Melanoma, Thyroid, Cervical | mTORC2/SREBP1 signaling | In vitro | [39] | ||
Tumor suppressor | T cell leukemia | Notch signaling | In vitro, In vivo | [40] | ||
Tumor suppressor | Colorectal | c-Myc signaling, Cell cycle | In vitro | [41] | ||
Tumor suppressor | Esophageal squamous cell | c-Myc signaling | In vitro | [42] | ||
Tumor suppressor | Colorectal, Cervical, Ovarian, Non-small cell lung | Apoptosis (via Mcl1) | In vitro | [43] | ||
MDM2 | Oncogene | Neuroblastoma | p53 signaling | In vitro, In vivo | [44] | |
Oncogene | Cervical | Cell cycle, Apoptosis | In vitro | [45] | ||
Oncogene | Liver | Metastasis, Drug response | In vitro, In vivo | [46] | ||
Cdc20 | Oncogene | Breast | Metastasis, Drug response | In vitro | [47] | |
Cdh1 | Tumor suppressor | Breast | Src signaling | In vitro | [48] | |
β-TRCP | Tumor suppressor | Breast, Prostate | MTSS1 signaling | In vitro | [49] | |
Oncogene | Lung | FOXN2 | In vitro, In vivo | [50] | ||
Tumor suppressor | Papillary thyroid | VEGFR2 signaling | In vitro, In vivo | [51] | ||
E6AP | Oncogene | Prostate | Radiation response | In vitro | [52] | |
Oncogene | Prostate | p27 signaling | In vitro, In vivo | [53] | ||
Oncogene | Prostate | Metastasis | In vitro, In vivo | [54] |
Name | Role | Cancer Type | Function | Test model | Reference |
BAP1 | Tumor suppressor | Lung, Osteosarcoma, Colon | DNA double-strand repair | In vitro | [61][62][63] |
Tumor suppressor | Renal | Ferroptosis signaling | In vitro | [64] | |
USP7 | Oncogene | Lung | p53 signaling | In vitro, in vivo | [65] |
Oncogene | Cervical | Self-renewal; Foxp3 signaling | In vitro | [66] | |
Oncogene | Non-small cell lung | Immune Response; Foxp3 signaling | In vitro | [67] | |
USP22 | Oncogene | Lung | Cell Cycle | In vitro | [68] |
Oncogene | Lung adenocarcinoma | EGFR-TKI resistance | In vitro, in vivo | [69] | |
Oncogene | Colon | CCNB1 signaling | In vitro, in vivo | [70] | |
Oncogene | Glioblastoma | KDM1A signaling | In vitro, in vivo | [71] | |
UCHL1 | Oncogene | Breast | Drug resistance; Invasion/migration | In vitro | [72] |
Ataxin 3 | Oncogene | Breast, Osteosarcoma, Cervical, Colorectal | DNA | In vitro | [73] |
Oncogene | Testicular | mTOR/Akt signaling | In vitro | [74] | |
PSMD11 | Oncogene | Cervical. Osteosarcoma | DNA damage response | In vitro | [75] |
Oncogene | Lung, Prostate, Colorectal, Breast, Cervix | Cell cycle | In vitro | [76] | |
Oncogene | Liver | E2F1 signaling | In vitro, in vivo | [77] | |
A20 | Tumor suppressor | Colorectal | Apoptosis signaling | In vitro | [78] |
Tumor suppressor | Diffuse large B-cell lymphoma | NF-kβ signaling | In vitro | [79] | |
Tumor suppressor | Sarcoma | NF-kβ signaling | In vitro | [80] |
Inhibitor | Target | Cancer Type | Clinical Trial | Reference |
---|---|---|---|---|
Bortezomib | Proteasomal inhibitor | Multiple myeloma, Mantle cell lymphoma, Leukemia, Neuroblastoma, Head and Neck, Thyroid, Hepatocellular |
FDA approved | www.clinicaltrials.gov [81][82][83][84][85][86][87][88] |
Carfilzomib | Proteasomal inhibitor | Multiple myeloma, Lymphoma, Relapsed and/or refractory multiple myeloma, Leukemia, Lung, Thyroid, Refractory renal cell carcinoma |
FDA approved | www.clinicaltrials.gov [52][89][90][91][92][88] |
Ixazomib | Proteasomal inhibitor | Multiple myeloma, Relapsed and/or refractory multiple myeloma, Lymphoma, Leukemia, Breast, Glioblastoma, Renal cell carcinoma, Hodgkin and T cell lymphoma |
FDA approved | www.clinicaltrials.gov [93] |
Delanzomib | Proteasomal inhibitor | Non-Hodgkin’s lymphoma | Phase I | www.clinicaltrials.gov |
Marizomib | Proteasomal inhibitor | Multiple myeloma, Advanced solid tumors | Phase I/II | www.clinicaltrials.gov |
Oprozomib | Proteasomal inhibitor | Multiple myeloma, Glioma, Pancreatic, Lung, Melanoma, Lymphoma, Glipblastoma | Phase I/II/III | www.clinicaltrials.gov |
MLN4924 | NAE and UBA1(E1) | Advanced malignant solid tumors, Melanoma, Hepatocellular, B cell lymphoma, Hematologic malignancies, Acute myelocytic leukemia |
Phase I/II/III | www.clinicaltrials.gov |
TAK981 | SAE (E1) | B cell lymphoma, colorectal, non-Hodgkin’s, Advcnced/metasiatic solid tumors | Phase I/II | www.clinicaltrials.gov |
TAS4464 | NAE (E1) | Multiple myeloma, non-Hodgkin lymphoma | Phase I/II | www.clinicaltrials.gov |
SAR-405838 | MDM2 (E2) | Solid tumors | Phase I | www.clinicaltrials.gov [87][94] |
CGM-097 | MDM2 (E2) | Advanced p53 wildtype solid tumors | Phase I | www.clinicaltrials.gov [95][96] |
DS-3032b | MDM2 (E2) | Acute myelocytic leukemia | Phase I/II | www.clinicaltrials.gov [97][98] |
Debio1143 (AT-406) | cIAP1/2 (E3) | Acute myeloid leukemia | Phase I | www.clinicaltrials.gov [99] |
LC-161 | IAP (E3) | Advanced solid tumors | Phase I | www.clinicaltrials.gov [100] |
Birinapant | IAP (E3) | Solid tumors | Phase I/II | www.clinicaltrials.gov [101] |
Pimozide | USP1 | Glioma, Non-small cell lung cancer | FDA approced for Tourette’s syndrome; Preclinical | [102][103] |
Mitoxantrone | USP11 | Metastatic crastrate -resistant prostate, Acute myeloid leukemia, Advanced breast cancer, non-Hodgkin’s lymphoma, Primary liver |
FDA approved | [104][105][106][107][108][109][110][111][112] |
This entry is adapted from the peer-reviewed paper 10.3390/cancers13071513