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* INSERM U716, Equipe AVENIR, Institut de Génétique Moléculaire, Paris; Université Paris 7, Paris, France;
Diseases of Aging Program, Ottawa Health Research Institute, Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada; and
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada
1Correspondence: Laboratoire de Pharmacologie Expérimentale et Clinique, INSERM U716/ Equipe AVENIR, Institut de Génétique Moléculaire, 27 rue Juliette Dodu, 75010 Paris, France. E-mail: majid.khatib{at}stlouis.inserm.fr
The 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.—Scamuffa, N., Calvo, F., Chrétien, M., Seidah, N. G., Khatib, A-M. Proprotein convertases: lessons from knockouts.
Key Words: abnormal embryonic development • hormonal disorder • cellular proliferation • infertility • dyslipidemias • human patients
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