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Proprotein convertases: lessons from knockouts. 2006

Nathalie Scamuffa, and Fabien Calvo, and Michel Chrétien, and Nabil G Seidah, and Abdel-Majid Khatib
INSERM U716/ Equipe AVENIR, Institut de Génétique Moléculaire, 27 rue Juliette Dodu, 75010 Paris, France.

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.

UI MeSH Term Description Entries
D002319 Cardiovascular System The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body. Circulatory System,Cardiovascular Systems,Circulatory Systems
D004622 Embryo, Mammalian The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS. Embryonic Structures, Mammalian,Mammalian Embryo,Mammalian Embryo Structures,Mammalian Embryonic Structures,Embryo Structure, Mammalian,Embryo Structures, Mammalian,Embryonic Structure, Mammalian,Embryos, Mammalian,Mammalian Embryo Structure,Mammalian Embryonic Structure,Mammalian Embryos,Structure, Mammalian Embryo,Structure, Mammalian Embryonic,Structures, Mammalian Embryo,Structures, Mammalian Embryonic
D006331 Heart Diseases Pathological conditions involving the HEART including its structural and functional abnormalities. Cardiac Disorders,Heart Disorders,Cardiac Diseases,Cardiac Disease,Cardiac Disorder,Heart Disease,Heart Disorder
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013379 Substrate Specificity A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D043484 Proprotein Convertases Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES. Pro-Opiomelanocortin Converting Enzyme,Prohormone Convertases,Proprotein Convertase,POMC Convertase,POMC Enzyme,POMC-Converting Enzyme,Pro-Opiocortin Converting Enzyme,Pro-Opiocortin Converting Protease,Prohormone Convertase,Proopiomelanocortin Convertase,Proprotein Convertase, Subtilisin-Kexin Family,Proprotein Convertases, Subtilisin-Kexin Family,Subtilisin-Like Proprotein Convertases,Convertase, POMC,Convertase, Prohormone,Convertase, Proopiomelanocortin,Convertase, Proprotein,Convertases, Prohormone,Convertases, Proprotein,Convertases, Subtilisin-Like Proprotein,Converting Enzyme, Pro-Opiocortin,Converting Enzyme, Pro-Opiomelanocortin,Converting Protease, Pro-Opiocortin,POMC Converting Enzyme,Pro Opiocortin Converting Enzyme,Pro Opiocortin Converting Protease,Pro Opiomelanocortin Converting Enzyme,Proprotein Convertase, Subtilisin Kexin Family,Proprotein Convertases, Subtilisin Kexin Family,Proprotein Convertases, Subtilisin-Like,Subtilisin Like Proprotein Convertases
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018345 Mice, Knockout Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes. Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out

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