Linked Life Data

17351764

Source:http://linkedlifedata.com/resource/pubmed/id/17351764

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-7-16
pubmed:abstractText
The family of the secretory proprotein convertases (PCs) comprises seven basic amino acid (aa)-specific subtilisin-like serine proteinases known as PC1/3, PC2, furin, PC4, PC5/6, PACE4 and PC7, and two other PCs, SKI-1 (subtilisin-kexin isozyme-1)/S1P (site-1 protease) and PCSK9 (proprotein convertase subtilisin kexin 9) that cleave at nonbasic residues. Except for the testicular PC4, all the other convertases are expressed in brain and peripheral organs and play a critical role in various functions including the production of diverse neuropeptides as well as growth factors and receptors, the regulation of cellular adhesion/migration, cholesterol and fatty acid homeostasis, and growth/differentiation of progenitor cells. Some of these convertases process proteins that are implicated in pathologies, including cancer malignancies, tissue regeneration, and viral infections. The implication of some of these convertases in sterol/lipid metabolism has only recently been appreciated. SKI-1/S1P activates the synthesis of cholesterol and fatty acids as well as the LDL receptor (LDLR), whereas PCSK9 inactivates the LDLR. Moreover, furin, PC5 and/or, PACE4 inactivates endothelial and lipoprotein lipases. Humans and mice exhibiting either a gain or loss of function of PCSK9 through specific point mutations or knockouts develop hypercholesterolemia and hypocholesterolemia phenotypes, respectively. A PCSK9 inhibitor in combination with statins offers a most promising therapeutic target to treat cardiovascular disorders including dyslipidemias. Specific inhibitors/modulators of the other PCs should find novel therapeutic applications in the control of PC-regulated pathologies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0946-2716
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
685-96
pubmed:dateRevised
2011-7-8
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The proprotein convertases are potential targets in the treatment of dyslipidemia.
pubmed:affiliation
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal, Quebec, H2W 1R7, Canada. seidahn@ircm.qc.ca
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't