Molecular biology of PCSK9: its role in LDL metabolism
Open accessAbstract
Proprotein convertase subtilisin-like kexin type 9 (PCSK9) is a newly discovered serine protease that destroys low density lipoprotein (LDL) receptors in liver and thereby controls the level of LDL in plasma. Mutations that increase PCSK9 activity cause hypercholesterolemia and coronary heart disease (CHD); mutations that inactivate PCSK9 have the opposite effect, lowering LDL levels and reducing CHD. Although the mechanism of PCSK9 action is not yet clear, the protease provides a new therapeutic target to lower plasma levels of LDL and prevent CHD.
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PCSK9 and IDOL are well-established post-translational regulators of LDLR turnover.
“Although PCSK9 (ref. 8) and IDOL 9 are well-established post-translational regulators of LDLR turnover, the mechanisms controlling LDLR trafficking and degradation are not yet fully understood, especially in response to high dietary cholesterol.”
From Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover (2026) · cites this paper as [8]
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- Authors
- HORTON, J., COHEN, J., & HOBBS, H.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- HORTON, J
- HOBBS, H
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 32
- Issue
- 2
- Pages
- 71-77
- ISSN
- 0968-0004 (ISSN-L)
- PMC
- PMC2711871
- OpenAlex
- W2141191772
- Cited by
- 621
- References
- 2
- Citations by year
- 2026: 22 · 2025: 38 · 2024: 33 · 2023: 30 · 2022: 38 · 2021: 40 · 2020: 21 · 2019: 33 · 2018: 34 · 2017: 29 · 2016: 36 · 2015: 39 · 2014: 28 · 2013: 30 · 2012: 33
- FWCI
- 36.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01 HL 2098, P01HL020948)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- PCSK9, LDL receptor degradation, LDL metabolism, hypercholesterolemia, coronary artery disease, PCSK9 mutations, PCSK9 inhibitors, serine protease, plasma LDL cholesterol
- MeSH terms
- Proprotein Convertase 9, Coronary Disease, Humans, Hypolipoproteinemias, Cholesterol, LDL, Molecular Biology, Serine Endopeptidases, Genetic Variation, Proprotein Convertases
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