The proprotein convertases and their implication in sterol and/or lipid metabolism.
The proprotein convertases represent a family of nine proteinases, comprising seven basic amino acid-specific subtilisin-like serine proteinases related to yeast kexin, known as PC1/3, PC2, furin, PC4, PC5/6, PACE4 and PC7, and two other subtilases that cleave at non-basic residues, called SKI-1/S1P and NARC-1/PCSK9. The present review concentrates on the regulatory role played by some of these convertases in cholesterol and lipid metabolism. Thus, PC5/6, PACE4 and Furin upregulate high-density lipoprotein (HDL) levels via the inactivation of endothelial and lipoprotein lipases. The SKI-1/S1P-directed cleavage of membrane-bound transcription factors known as sterol regulatory element binding proteins (SREBP-1 and SREBP-2) results in upregulation of the synthesis of sterols, lipids and the LDL receptor (LDLR). Finally, PCSK9 downregulates the protein levels of the LDLR by enhancement of its intracellular metabolic pathway in subcellular acidic compartments.
Seidah
Nabil G
NG
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave. West, Montreal H2W 1R7, QC, Canada. nabil.seidah@ircm.qc.ca
Khatib
Abdel Majid
AM
Prat
Annik
A
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D006868:Hydrolysis; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D008969:Molecular Sequence Data; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000737:chemistry / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D013261:Sterols / Q000378:metabolism*
D011973:Receptors, LDL; D013261:Sterols; D008049:Lipase; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C115575:membrane-bound transcription factor peptidase, site 1