title: Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets.
abstract: The ubiquitin-proteasome system (UPS) and ubiquitin-like protein (UBL) conjugation pathways are integral to cellular protein homeostasis. The growing recognition of the fundamental importance of these pathways to normal cell function and in disease has prompted an in-depth search for small-molecule inhibitors that selectively block the function of these pathways. However, our limited understanding of the molecular mechanisms and biological consequences of UBL conjugation is a significant hurdle to identifying drug-like inhibitors of enzyme targets within these pathways. Here, we highlight recent advances in understanding the role of some of these enzymes and how these new insights may be the key to developing novel therapeutics for diseases including immuno-inflammatory disorders, cancer, infectious diseases, cardiovascular disease and neurodegenerative disorders.
authors.affiliation: School of Biomedical Sciences, University of Nottingham, Nottingham, UK. james.brownell@mpi.com
authors.forename: Lynn
authors.initials: L
authors.lastname: Bedford
authors.forename: James
authors.initials: J
authors.lastname: Lowe
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Dick
authors.forename: R John
authors.initials: RJ
authors.lastname: Mayer
authors.forename: James E
authors.initials: JE
authors.lastname: Brownell
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D025801:Ubiquitin; D014452:Ubiquitins; D046988:Proteasome Endopeptidase Complex