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Proprotein convertases: lessons from knockouts Scamuffa N; Calvo F; Chretien M; Seidah NG; Khatib AMFASEB J 2006[Oct]; 20 (12): 1954-63The physiological role of the subtilisin/kexin-like proprotein convertases (PCs) in rodents has been examined through the use of knockout mice. This review will summarize the major in vivo defects that result from the disruption of the expression of their genes. This includes abnormal embryonic development, hormonal disorder, infertility, and/or modified lipid/sterol metabolism. Members of the PC family play a central role in the processing of various protein precursors ranging from hormones and growth factors to bacterial toxins and viral glycoproteins. Proteolysis occurring at basic residues is mediated by the basic amino acid-specific proprotein convertases, namely: PC1/3, PC2, furin, PACE4, PC4, PC5/6, and PC7. In contrast, proteolysis at nonbasic residues is performed by the subtilisin/kexin-like isozyme-1 (SKI-1/S1P) and the newly identified neural apoptosis-regulated convertase-1 (PCSK9/NARC-1). In addition to their requirement for many physiological processes, these enzymes are also involved in various pathologies such as cancer, obesity, diabetes, lipid disorders, infectious diseases, atherosclerosis and neurodegenerative diseases.|Animals[MESH]|Cardiovascular System/embryology/growth & development[MESH]|Embryo, Mammalian[MESH]|Heart Diseases/enzymology/etiology[MESH]|Mice[MESH]|Mice, Knockout[MESH]|Proprotein Convertases/antagonists & inhibitors/deficiency/metabolism/*physiology[MESH]|Substrate Specificity[MESH] |
