Linking Ubiquitin Research to Drug Discovery

Gastrointestinal, Hepatic and Renal

Across the wide range of cell types found in the intestine, liver and kidneys, the common need for adequate control of protein homeostasis is clear. Pathologies occurring in these tissues are increasingly being linked to aspects of not only the ubiquitin cascade but also cell signalling in general.

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 targets expressed by tissue type 71

 

Digestive system
DUBs: AMSH-LP, BRCC3, MPND, USP12, YOD1

Liver and Biliary system
DUBs: Cezanne, MPND, OTUB2, USP18, USP26, USP29, USP30, USP31, USP35, USP40, USP43
E3 Ligases: Cul1/Rbx1, Cul1/Skp1/Rbx1, IDOL, ITCH, RNF8

Renal system
DUBs: OTUD3, USP2, USP21, USP45
E3 Ligases: Cul1/Rbx1Cul1/Skp1/Rbx1, DCNL1, ITCH

Ubiquitin system targets in diseases of the GI system, Liver and Kidneys 71

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

 

Oesophageal cancer
DUBs: ↑ USP17,USP46

Gastric cancers
DUBs: ↓ AMSH, ↑ USP1
E3 Ligase: Cul1/Skp1/Rbx1 68

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 70

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] 60, ↓ 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

Glomerulonephritis
DUB: ↑ OTUB1 51

Diabetes
DUB: OTUB2 50

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

Click here for reference list