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PMID: 23775089 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

The multifaceted proprotein convertases: their unique, redundant, complementary, and opposite functions.

The Journal of biological chemistry ·Vol. 288 ·No. 30 ·2013-07-26 ·Pages 21473-81

Seidah NG, Sadr MS, Chrétien M, Mbikay M

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.

Keywords
Cardiovascular Disease Cell Surface Receptor Cholesterol Metabolism Furin-like Protease Intracellular Processing Low Density Lipoprotein (LDL) Precursor Processing Proprotein Convertase Protease Secretory Proteins
MeSH Terms
Animals Cholesterol/metabolism Humans Mice Mice, Knockout Multigene Family Proprotein Convertases/genetics,metabolism Receptors, LDL/metabolism Substrate Specificity Subtilisins/genetics,metabolism
Chemicals
Receptors, LDL Cholesterol PCSK7 protein, human Pcsk7 protein, mouse Proprotein Convertases Subtilisins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Seidah Nabil G
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
Sadr Mohamad S
Chrétien Michel
Mbikay Majambu
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.R113.481549
Email
seidahn@ircm.qc.ca
Published
2013-07-26
Epub
2013-00-17
Pages
21473-81
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC3724608
Subset
IM
Grants
Canadian Institutes of Health Research · MOP-102618 · Canada
Canadian Institutes of Health Research · MOP-102741 · Canada
Canadian Institutes of Health Research · MOP-44363 · Canada
Canadian Institutes of Health Research · MOP-93792 · Canada
External Links
PubMed source DOI: 10.1074/jbc.R113.481549 PMC Full Text View journal details
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