Linking Ubiquitin Research to Drug Discovery

Oncology

Uncontrolled cellular division is a hallmark of tumours, underlined by dysregulation of cell division, apoptosis and response to growth factors. The microenvironments of tumours may display altered cellular metabolisms and increased proteasomal activity. Many aspects of cellular dysregulation and opportunities for therapeutic intervention in oncology involve aspects of the ubiquitin cascade such as the regulation of oncogene and tumour suppressor turnover.

This is not intended to be an exhaustive list of targets and disease associations but one that highlights some of the most recent work in a variety of therapeutic areas. There are other targets across the ubiquitin system that may be added to this list as well as further therapeutic applications of those already referenced – why not let us know of key ubiquitin system therapeutic associations that you have seen or are working on and help us build this resource. Submit your suggestions here.

Click here for reference list.

Ubiquitin system associated targets in Oncology 71

↓ – down regulated, ↑ – over-expressed, [ ] – mutated

 

Breast cancer
DUBs: ↑ Cezanne 65, [CSN6], [EIF3H], ↑ OTUB2, ↓ USP2, ↑ USP14, USP11 62, 63, [USP15], ↓ USP16, ↓ USP22, ↑ USP22, ↓ USP24,
USP28 43, ↑ USP32, USP35 64, ↓ USP44, ↓ USP46, ↓ USP47, ↓ USP53
E2 Conjugating enzymes: Ube2Q1 86, Ube2Q2 87
E3 Ligases: WWP1 17, SMURF1 18, SMURF2 18

Cervical cancer
DUBs: ↑ USP17, UCHL3 48
E2 Conjugating enzyme: Ube2S 88
E3 Ligase: ↑ BIRC2 9

Ovarian cancer
DUBs: ↑ USP2, ↑ USP14, ↓ USP15, [USP15], [USP34], ↑ USP36 44, OTU1 49

Lung (NSCLC)
DUBs: ↑ CSN5, ↑ JOSD1, ↓ OTUD1, ↓ USP1 28, ↑ USP4USP8 58, ↑ USP9x, ↑ USP17, ↓ USP25 42, ↓ USP53, ↑ UCHL1
E2 conjugating enzymes: Ube2C 82, Ube2I 84, Ube2T 89
E3 Ligases: RNF8 16

Lung (SCLC)
DUBs: ↑ USP4, ↓ USP4

Lymphoma
DUBs: ↓ A20, ↓ JOSD1, ↓ OTUD1, ↓ USP22, ↓ USP28, ↓ USP34, ↓ USP36, ↓ USP53, ↓ USPL1, [PRPF8], [USP9x], ↑ BRCC3, ↑ USP31

Melanoma
DUBs: [BAP1], ↑ CSN5, USP8 57, ↑ USP10, ↑ USP11, ↑ USP22, ↑ USP48
E3 Ligases: Cul1/Rbx1 67, Cul1/Skp1/Rbx1 67

Skin cancer
DUBs: [Ataxin-3L], [Cezanne2], [CYLD45, [USP17], [MYSM1], [PRPF8], [USP2], [USP4], [USP5], [USP6], [USP7], [USP8], [USP9x], [USP9Y], [USP13], [USP19], [USP25], [USP26], [USP28], [USP29], [USP31], [USP32], [USP34], [USP36], [USP37], [USP42], [USP44], [USP47], [USP48], ↓ USP49, [USP51], [USPL1], [VCPIP1]

Prostate cancer
DUB: USP2 30

Myeloma
DUB: USP7 33
E3 Ligase: [CBL] 74
Proteasome (protease catalytic sites) 77, 78

Pancreatic cancer
DUB: USP9x 34

Brain cancers
DUBs: ↓ Cezanne2, ↓ UCHL1, ↑ USP1, ↑ USP3, ↓ USP11, [USP15]
E3 Ligase: CHIP 7

Oesophageal cancer
DUBs: ↑ USP17,USP46

Gastric cancers
DUBs: ↓ AMSH, ↑ USP1

Large Intestine cancers
DUBs: [A20], [Ataxin-3L], [Cezanne], [Cezanne2], [USP17], [MYSM1], [OTUD3], [OTUD4], [USP2], [USP3], [USP4], [USP5], [USP6], [USP7], [USP8], [USP9x], [USP9Y], [USP11], [USP13], [USP16], [USP19], [USP21], [USP25], [USP26], [USP28], [USP29], [USP31], [USP32], [USP33], [USP34], [USP36], [USP42], [USP44], [USP45], [USP47], [USP48], ↓ USP49, [USP51], [USP54], [USPL1], [VCPIP1]

Colorectal cancer
DUBs: ↑ AMSH-LP, ↓ Cezanne, ↑ EIF3H, ↓ MPND, ↓ JOSD1, ↓ OTUD1, ↑ OTUD6B, ↑ OTUB2, ↓ UCHL1, ↑ UCHL1 47, ↑ UCHL3, ↓ USP2, USP9x 35, ↑ USP10, ↑ USP14 37, ↑ USP17, ↑ USP22, ↓ USP53, ↑ USPL1
E3 Ligase: RNF8

Liver cancer
DUBs: [PRPF8], ↑ USP14 36, [USP25], [USP38], [USP40]
E3 Ligase: SMURF1 20

Urinary Tract cancers
DUBs: [USP2], [USP4], [USP5], [USP26], [USP48], [VCPIP1]

Renal cancer
DUBs: ↑ AMSH-LP, [BAP1], ↓ UCHL1, ↓ USP2, ↓ USP5, ↑ USP14, ↑ USP34, ↓ USP46
E3 Ligases: Cul3/Rbx1 13, Cul5/Rnf7 11

Bladder cancer
DUBs: ↑ OTUB1, ↑ USP4, USP2 29
E3 Ligase: Cul3/Rbx1 12

Leukaemia
DUBs: [BRCC3], ↓ USP1, ↑ USP11, ↑ USP13, ↑ USP46
E3 Ligases: TRIAD 23, [CBL] 75, 76Cul5/Rnf7 10

Haematopoietic cancers
DUB: [USP9x]

↓ – down regulated, ↑ over-expressed, [ ] – mutated

Click here for reference list.