Strategies for the identification of ubiquitin ligase inhibitors.
Dysregulation of the UPS (ubiquitin-proteasome system) has been implicated in a wide range of pathologies including cancer, neurodegeneration and viral infection. Inhibiting the proteasome has been shown to be an effective therapeutic strategy in humans; however, toxicity with this target remains high. E3s (Ub-protein ligases) represent an alternative attractive therapeutic target in the UPS. In this paper, we will discuss current platforms that report on E3 ligase activity and can detect E3 inhibitors, and underline the advantages and disadvantages of each approach.
Goldenberg
Seth J
SJ
Progenra Inc., 271A Great Valley Parkway, Malvern, PA 19355, USA. goldenberg@progenra.com
Marblestone
Jeffrey G
JG
Mattern
Michael R
MR
Nicholson
Benjamin
B
D001681:Biological Assay / Q000379:methods; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy / Q000201:enzymology; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology; D011480:Protease Inhibitors / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex