PCSK9: a convertase that coordinates LDL catabolism

  1. Helen H. Hobbs 1 ,* §
  1. *Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046
  2. Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046
  3. §The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046
  1. 1To 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.

Footnotes

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

    • 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

  • Received November 19, 2008.
  • Revision received November 19, 2008.
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  1. The Journal of Lipid Research, 50, S172-S177.
  1. All Versions of this Article:
    1. R800091-JLR200v1
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