Abstract：
:Ubiquitination is a highly conserved post-translational modification that regulates protein trafficking, function, and turnover. Ubiquitin ligases (E3s) conjugate ubiquitin polypeptides on substrates, whereas deubiquitnases (DUBs) reverse ubiquitination. Engineering of chemical antagonists and inhibitors of ubiquitin ligases and DUBs has considerably aided the study of enzymes that participate in ubiquitin modification of substrates. In addition, proteomic tools have been developed to characterize the enzymes, substrates, and modifications regulated by DUBs and E3s. Here we review inhibitors and antagonists that have been developed against DUBs and E3s, focusing on enzymes that participate in ubiquitin editing or in the reciprocal ubiquitin regulation of substrates. We outline the cellular biology that is regulated by these DUBs and E3s and highlight how the inhibitory compounds have improved our understanding of these pathways. Finally, we discuss the challenges and future directions for pharmacologically targeting ubiquitin-modifying enzymes, as well as the development of proteomic methods to evaluate ubiquitin modification of substrates.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Lill JR,Wertz IEdoi
10.1016/j.tips.2014.01.005subject
Has Abstractpub_date
2014-04-01 00:00:00pages
187-207issue
4eissn
0165-6147issn
1873-3735pii
S0165-6147(14)00017-0journal_volume
35pub_type
杂志文章,评审abstract：:Data sets from recent large-scale projects can be integrated into one unified puzzle that can provide new insights into how drugs and genetic perturbations applied to human cells are linked to whole-organism phenotypes. Data that report how drugs affect the phenotype of human cell lines and how drugs induce changes in...
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