Small-Molecule Inhibitors and Probes for Ubiquitin- and Ubiquitin-Like-Specific Proteases

摘要

The post-translational modification of proteins with ubiquitin (Ub) or ubiquitin-like (Ubl) modifiers is an important signal in the regulation of a variety of biological processes.The attachment of either a single Ub,a 76 amino acid polypeptide,or multiple Ub entities helps to control the targeting of substrates for degradation.Processes such as receptor internaliza-tion,trafficking to the lysosomal compartments,and regulation of gene expression are likewise affected by Ub conjugation.Ubiquitin-like modifiers also play a role in protein targeting and in the regulation of protein function.For instance,the small Ubl modifier SUMO,a 97 amino acid polypeptide,functions as a nuclear targeting signal,amongst other functions.Nedd8,another polypeptide with pomology to Ub,regulates the activity of E3 ligases,thereby influencing the ubiquitylation process.In addition,a family of Ub related proteins,referred to as APGs,has been shown to control autophagy.