Proteases: Pivot Points in Functional Proteomics.
Proteases drive the life cycle of all proteins, ensuring the transportation and activation of newly minted, would-be proteins into their functional form while recycling spent or unneeded proteins. Far from their image as engines of protein digestion, proteases play fundamental roles in basic physiology and regulation at multiple levels of systems biology. Proteases are intimately associated with disease and modulation of proteolytic activity is the presumed target for successful therapeutics. "Proteases: Pivot Points in Functional Proteomics" examines the crucial roles of proteolysis across a wide range of physiological processes and diseases. The existing and potential impacts of proteolysis-related activity on drug and biomarker development are presented in detail. All told the decisive roles of proteases in four major categories comprising 23 separate subcategories are addressed. Within this construct, 15 sets of subject-specific, tabulated data are presented that include identification of proteases, protease inhibitors, substrates, and their actions. Said data are derived from and confirmed by over 300 references. Cross comparison of datasets indicates that proteases, their inhibitors/promoters and substrates intersect over a range of physiological processes and diseases, both chronic and pathogenic. Indeed, "Proteases: Pivot Points …" closes by dramatizing this very point through association of (pro)Thrombin and Fibrin(ogen) with: hemostasis, innate immunity, cardiovascular and metabolic disease, cancer, neurodegeneration, and bacterial self-defense.
['Verhamme|Ingrid M|IM|', 'Leonard|Sarah E|SE|', 'Perkins|Ray C|RC|']
D000818:Animals D003165:Complement System Proteins D004198:Disease Susceptibility D055808:Drug Discovery D006801:Humans D056747:Immunomodulation D010447:Peptide Hydrolases D011480:Protease Inhibitors D059748:Proteolysis D020543:Proteome D040901:Proteomics D000074702:Proteostasis D015398:Signal Transduction D013379:Substrate Specificity
Protease Digestion Proteolysis Biomarker development Protease inhibitor Hemostasis Metabolic disease Cancer Autoimmune disease Cardiovascular disease Cell migration Cell proliferation Complement system Cytosolic proteolysis DNA processing DNA repair DNA replication Drug development Drug target Epigenetics Immune regulation Infectious organisms Inflammation Intramembrane proteolysis Intranuclear proteolysis Neurodegenerative disease Peptidase Precision medicine Programmed cell death Protease promoter Protein secretion Signaling Stroke Transmembrane proteolysis