title: Mechanisms, biology and inhibitors of deubiquitinating enzymes.
abstract: The addition of ubiquitin (Ub) and ubiquitin-like (Ubl) modifiers to proteins serves to modulate function and is a key step in protein degradation, epigenetic modification and intracellular localization. Deubiquitinating enzymes and Ubl-specific proteases, the proteins responsible for the removal of Ub and Ubls, act as an additional level of control over the ubiquitin-proteasome system. Their conservation and widespread occurrence in eukaryotes, prokaryotes and viruses shows that these proteases constitute an essential class of enzymes. Here, we discuss how chemical tools, including activity-based probes and suicide inhibitors, have enabled (i) discovery of deubiquitinating enzymes, (ii) their functional profiling, crystallographic characterization and mechanistic classification and (iii) development of molecules for therapeutic purposes.
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: Kerry Routenberg
authors.initials: KR
authors.lastname: Love
authors.forename: André
authors.initials: A
authors.lastname: Catic
authors.forename: Christian
authors.initials: C
authors.lastname: Schlieker
authors.forename: Hidde L
authors.initials: HL
authors.lastname: Ploegh
mesh_terms: D000818:Animals; D001695:Biology; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D010802:Phylogeny; D064570:Ubiquitin-Specific Proteases
chemical_list: D004791:Enzyme Inhibitors; D010450:Endopeptidases; D064570:Ubiquitin-Specific Proteases