Therapeutic strategies within the ubiquitin proteasome system.
The ubiquitin-dependent proteolysis system (UPS) is the main driver of regulated protein degradation in all eukaryotic cells, and it is becoming increasingly clear that defects within this pathway drive a large number of human pathologies. Recent success in the use of proteasome inhibitors in the treatment of hematological malignancies validates the UPS as a viable therapeutic pathway, and substantial effort is now focused on the development of both second-generation proteasome inhibitors as well as novel strategies for the inhibition of upstream UPS enzymes. In this review we discuss the potential 'druggability' of key nodes within the UPS and summarize recent advances within the field.
Eldridge
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AG
Department of Cell Regulation, Genentech Inc., South San Francisco, CA 94080, USA. eldridge.adam@gene.com
O'Brien
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T
D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D025801:Ubiquitin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
D004791:Enzyme Inhibitors; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex