Strategies for the identification of ubiquitin ligase inhibitors

Biochem Soc Trans. 2010 Feb;38(Pt 1):132-6. doi: 10.1042/BST0380132.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Biological Assay / methods
  • Humans
  • Immune System Diseases / drug therapy
  • Immune System Diseases / enzymology
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / enzymology
  • Protease Inhibitors / metabolism*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors*
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / antagonists & inhibitors*
  • Ubiquitin-Protein Ligases / metabolism


  • Protease Inhibitors
  • Proteasome Inhibitors
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex