title: Proteomic identification of protease cleavage sites: cell-biological and biomedical applications.
abstract: Proteolysis shapes proteomes by protein degradation or restricted proteolysis, which generates stable cleavage products. Proteolytic (in-)activation of enzymes and cytokines is an essential aspect of the functional proteome status. Proteome-wide identification and quantification of proteolytic processing is accessible by complementary techniques for the focused analysis of protein termini. These innovative strategies are now widely applied and have transformed protease research. Pioneering studies portrayed apoptotic and caspase-dependent cleavage events. Protease-centric investigations focused predominantly on matrix metalloproteinases (MMPs), granzymes and aspartyl and cysteine cathepsins. The first in vivo degradomic studies were performed with mice lacking either cysteine cathepsins or matrix metalloproteinases. Process-centric degradomic analyses investigated infectious processes and mitochondrial import. Peptidomic analyses yielded disease biomarkers representing cleavage fragments from bodily fluids. The diversity of degradomic endeavors illustrates the importance of portraying proteolytic processing in health and disease. The present review provides an overview of the current status of degradomic studies.
authors.affiliation: 1Department of Cardiovascular Surgery, University Heart Center Freiburg - Bad Krozingen, D-79194 Freiburg, Germany.
authors.forename: Hasmik
authors.initials: H
authors.lastname: Shahinian
authors.forename: Stefan
authors.initials: S
authors.lastname: Tholen
authors.forename: Oliver
authors.initials: O
authors.lastname: Schilling
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002403:Cathepsins / Q000378:metabolism; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D040901:Proteomics; D013379:Substrate Specificity; D008625:Tiopronin / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D008625:Tiopronin; D002403:Cathepsins; D010447:Peptide Hydrolases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D053804:Granzymes; D020169:Caspases; D020782:Matrix Metalloproteinases