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Originally published In Press as doi:10.1194/jlr.R800091-JLR200 on November 19, 2008

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Journal of Lipid Research, Vol. 50, S172-S177, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Lipoprotein Metabolism

PCSK9: a convertase that coordinates LDL catabolism

Jay D. Horton1,*,{dagger}, Jonathan C. Cohen* and Helen H. Hobbs1,*,{dagger},§

* Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046
{dagger} Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046
§ The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046

Published, JLR Papers in Press, November 19, 2008.

1 To whom correspondence should be addressed. e-mail: jay.horton{at}utsouthwestern.edu (J.D.H); helen.hobbs{at}utsouthwestern.edu (H.H.H.)


ABSTRACT

The identification and characterization of proprotein convertase subtilisin-like/kexin type 9 (PCSK9) have provided new insights into LDL metabolism and the causal role of LDL in coronary heart disease (CHD). PCSK9 is a secreted protease that mediates degradation of the LDL receptor by interacting with the extracellular domain and targeting the receptor for degradation. Individuals with loss-of-function mutations in PCSK9 have reduced plasma levels of LDL cholesterol and are protected from CHD; these observations have validated PCSK9 as a therapeutic target and suggested new approaches for the treatment and prevention of CHD.

Supplementary key words low density lipoprotein receptor • proprotein convertase subtilisin-like/kexin type 9 • low density lipoprotein • hypercholesterolemia

Abbreviations: CHD, coronary heart disease; EGF, epidermal growth factor; ER, endoplasmic reticulum; FH, familial hypercholesterolemia; LDL-C, LDL cholesterol; LDLR, LDL receptor; PCSK9, proprotein convertase subtilisin-like/kexin type 9; SREBP, sterol regulatory element binding protein


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Related Webpages:

JLR 50th Anniversary Collections
Anniversary Collection::Lipoprotein Metabolism

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