Mechanisms, biology and inhibitors of deubiquitinating enzymes

作者：Love Kerry Routenberg^*; Catic Andre; Schlieker Christian; Ploegh Hidde L

来源：Nature Chemical Biology, 2007, 3(11): 697-705.

DOI：10.1038/nchembio1107-695

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.

• 出版日期2007-11