Linking Ubiquitin Research to Drug Discovery

Cardiovascular, Inflammatory and Metabolic

Effective protein turnover is required for cardiac homeostasis, such that impaired proteasomal function is increasingly being linked to heart disease. Specific ubiquitin proteasomal and lysosomal degradation and non-degradative mechanisms underlying cardiovascular biology, inflammatory and metabolic disease have been identified and furthermore, many such cellular pathways have been proposed to be targets of clinical relevance; for example in the regulation of circulating low density lipoprotein.

Below we have included a list of some targets and disease associations that highlight 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

Targets expressed in Cardiovascular Tissue 71

 

Haematopoietic System
DUBs: A20AMSH-LP, CYLD, EIF3H, OTUD5, PRPF8, USP3, USP4, USP7, USP8, USP9Y, USP15, USP20, USP25, USP28, USP33, USP34, USP36, USP39, USPL1
E3 Ligases: CBL, TRIAD

Heart
DUBs: OTUB1, OTUD6A, USP13
E3 Ligases: Cul5/Rnf7, DCNL1IDOL, ITCH, MURF1

Ubiquitin associated targets in the haematopoietic system 71

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

 

Immunomodulation
DUBs: A20 54, Cezanne 64, OTUD5 52, OTULIN 55, USP4 31, USP20 41
E3 Ligases: IPAH9.8 69, ITCH 6
Ubiquitin Binding Proteins: [NEMO] 79

Rheumatoid Arthritis
E3 Ligase: Cul1/Rbx1 14

Lipid Homeostasis
DUBs: USP8 59
E3 Ligase: IDOL 1, 2, 59

Cardiomyopathy
DUBs: USP3, BRCC3
E3 Ligase: MURF1 25

Leukaemia
DUBs: [A20] 55, BAP1 61, [BRCC3], ↓ USP1, ↑ USP11, ↑ USP13, ↑ USP46
E3 Ligases: TRIAD 23, [CBL] 75, 76Cul5/Rnf7 10

Haematopoietic cancers
DUB: [USP9x]

Glomerulonephritis
DUB: ↑ OTUB1 51

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

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

Click here for reference list