Drug discovery in the ubiquitin–proteasome system
- 1 July 2006
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Drug Discovery
- Vol. 5 (7), 596-613
- https://doi.org/10.1038/nrd2056
Abstract
Regulated protein turnover via the ubiquitin–proteasome system (UPS) underlies a wide variety of signalling pathways, from cell-cycle control and transcription to development. Recent evidence that pharmacological inhibition of the proteasome can be efficacious in the treatment of human cancers has set the stage for attempts to selectively inhibit the activities of disease-specific components of the UPS. Here, we review recent advances linking UPS components with specific human diseases, most prominently cancer and neurodegenerative disorders, and emphasize potential sites of therapeutic intervention along the regulated protein-degradation pathway.Keywords
This publication has 100 references indexed in Scilit:
- Evasion of the p53 tumour surveillance network by tumour-derived MYC mutantsNature, 2005
- Function and regulation of cullin–RING ubiquitin ligasesNature Reviews Molecular Cell Biology, 2005
- Small molecule RITA binds to p53, blocks p53–HDM-2 interaction and activates p53 function in tumorsNature Medicine, 2004
- Small-molecule inhibitors of protein–protein interactions: progressing towards the dreamNature Reviews Drug Discovery, 2004
- Structure of a β-TrCP1-Skp1-β-Catenin Complex: Destruction Motif Binding and Lysine Specificity of the SCFβ-TrCP1 Ubiquitin LigaseMolecular Cell, 2003
- Structural basis for the recognition of hydroxyproline in HIF-1α by pVHLNature, 2002
- Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complexNature, 2002
- De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndromeNature Genetics, 1997
- UBE3A/E6-AP mutations cause Angelman syndromeNature Genetics, 1997
- Structure of ubiquitin refined at 1.8ÅresolutionJournal of Molecular Biology, 1987