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Licensed Unlicensed Requires Authentication Published by De Gruyter July 20, 2006

The proprotein convertases and their implication in sterol and/or lipid metabolism

  • Nabil G. Seidah , Abdel Majid Khatib and Annik Prat
From the journal Biological Chemistry

Abstract

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.

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Published Online: 2006-07-20
Published in Print: 2006-07-01

©2006 by Walter de Gruyter Berlin New York

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