title: Comprehensive profiling of protein ubiquitination for drug discovery.
abstract: Alterations of the ubiquitin proteasome system (UPS) contribute to the progression of many diseases, such as cancer, neurodegenerative diseases, immunological disorders, and inflammation. Pharmacologic inhibition of specific ubiquitin regulatory enzymes and ubiquitination events is an important challenge in drug discovery. Identifying the substrates of the various enzymes that participate in the UPS is needed to determine which enzymes are potential drug candidates. Additionally, identifying the ubiquitination events regulated by pharmacological drugs can potentially discover new applications. In this review we describe mass spectrometry-based proteomic approaches for the identification of ubiquitinated proteins and their modification sites on a proteome-wide scale, focusing on the ubiquitin remnant profiling, a newly developed ubiquitination profiling technique. We then discuss the application of this approach for the profiling of ubiquitination events regulated by cell signaling pathways and explore its future applications for drug discovery in the UPS.
authors.affiliation: Laboratory of Chemical Biology, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou Jiangsu 215123, China. gux2002@suda.edu.cn
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Xu
authors.forename: Samie R
authors.initials: SR
authors.lastname: Jaffrey
mesh_terms: D000818:Animals; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*; D057149:Ubiquitinated Proteins / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D025801:Ubiquitin; D057149:Ubiquitinated Proteins; D046988:Proteasome Endopeptidase Complex