title: Monitoring proteolytic processing events by quantitative mass spectrometry.
abstract: Protease activity plays a key role in a wide variety of biological processes including gene expression, protein turnover and development. misregulation of these proteins has been associated with many cancer types such as prostate, breast, and skin cancer. thus, the identification of protease substrates will provide key information to understand proteolysis-related pathologies. Areas covered: Proteomics-based methods to investigate proteolysis activity, focusing on substrate identification, protease specificity and their applications in systems biology are reviewed. Their quantification strategies, challenges and pitfalls are underlined and the biological implications of protease malfunction are highlighted. Expert commentary: Dysregulated protease activity is a hallmark for some disease pathologies such as cancer. Current biochemical approaches are low throughput and some are limited by the amount of sample required to obtain reliable results. Mass spectrometry based proteomics provides a suitable platform to investigate protease activity, providing information about substrate specificity and mapping cleavage sites.
authors.affiliation: a Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine , University of Pennsylvania , Philadelphia , PA , USA.
authors.forename: Mariel
authors.initials: M
authors.lastname: Coradin
authors.affiliation: a Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine , University of Pennsylvania , Philadelphia , PA , USA.
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Karch
authors.affiliation: a Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine , University of Pennsylvania , Philadelphia , PA , USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Garcia
mesh_terms: D000818:Animals; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism; D059748:Proteolysis; D040901:Proteomics / Q000379:methods*; D013379:Substrate Specificity
chemical_list: D010447:Peptide Hydrolases
keywords: Proteolysis; isotope labeling; mass spectrometry; protease; protease activity; proteomics; substrate recognition