title: Drug discovery in the ubiquitin-proteasome system.
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.
authors.affiliation: Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Nalepa
authors.forename: Mark
authors.initials: M
authors.lastname: Rolfe
authors.forename: J Wade
authors.initials: JW
authors.lastname: Harper
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex