title: The multifaceted proprotein convertases: their unique, redundant, complementary, and opposite functions.
abstract: The secretory proprotein convertase (PC) family comprises nine members: PC1/3, PC2, furin, PC4, PC5/6, PACE4, PC7, SKI-1/S1P, and PCSK9. The first seven PCs cleave their substrates at single or paired basic residues, and SKI-1/S1P cleaves its substrates at non-basic residues in the Golgi. PCSK9 cleaves itself once, and the secreted inactive protease escorts specific receptors for lysosomal degradation. It regulates the levels of circulating LDL cholesterol and is considered a major therapeutic target in phase III clinical trials. In vivo, PCs exhibit unique and often essential functions during development and/or in adulthood, but certain convertases also exhibit complementary, redundant, or opposite functions.
authors.affiliation: Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal (IRCM, affiliated with the University of Montreal), Montreal, Quebec H2W 1R7, Canada. seidahn@ircm.qc.ca
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
authors.forename: Mohamad S
authors.initials: MS
authors.lastname: Sadr
authors.forename: Michel
authors.initials: M
authors.lastname: Chrétien
authors.forename: Majambu
authors.initials: M
authors.lastname: Mbikay
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D043484:Proprotein Convertases / Q000235:genetics* / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism; D013379:Substrate Specificity; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism
chemical_list: D011973:Receptors, LDL; D002784:Cholesterol; C099101:PCSK7 protein, human; C490930:Pcsk7 protein, mouse; D043484:Proprotein Convertases; D013381:Subtilisins
keywords: Cardiovascular Disease; Cell Surface Receptor; Cholesterol Metabolism; Furin-like Protease; Intracellular Processing; Low Density Lipoprotein (LDL); Precursor Processing; Proprotein Convertase; Protease; Secretory Proteins