PCSK9

Summary

Gene Symbol: PCSK9
Description: proprotein convertase subtilisin/kexin type 9
Alias: FH3, HCHOLA3, LDLCQ1, NARC-1, NARC1, PC9, proprotein convertase subtilisin/kexin type 9, convertase subtilisin/kexin type 9 preproprotein, neural apoptosis regulated convertase 1, subtilisin/kexin-like protease PC9
Species: human

Top Publications

  1. ncbi Sequence variations in PCSK9, low LDL, and protection against coronary heart disease
    Jonathan C Cohen
    Donald W Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    N Engl J Med 354:1264-72. 2006
  2. ncbi Mutations in PCSK9 cause autosomal dominant hypercholesterolemia
    Marianne Abifadel
    INSERM U383, Hopital Necker Enfants Malades, AP HP, Universite Paris V, 149 161 Rue de Sèvres, 75743 Paris Cedex 15, France
    Nat Genet 34:154-6. 2003
  3. ncbi Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis
    Yue Wei Qian
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
    J Lipid Res 48:1488-98. 2007
  4. ncbi Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation
    Da Wei Zhang
    Department of Molecular Genetics, The Donald W Reynolds Cardiovascular Clinical Research Center, Howard Hughes Institute, University of Texas Southwestern Medical Center, Dallas 75390, USA
    J Biol Chem 282:18602-12. 2007
  5. ncbi The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2
    Steve Poirier
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 283:2363-72. 2008
  6. pmc A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol
    Ingrid K Kotowski
    McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, 75390 9046, USA
    Am J Hum Genet 78:410-22. 2006
  7. pmc Effects of the prosegment and pH on the activity of PCSK9: evidence for additional processing events
    Suzanne Benjannet
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 285:40965-78. 2010
  8. ncbi Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia
    Geneviève Dubuc
    Laboratory of Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Quebec, Canada
    Arterioscler Thromb Vasc Biol 24:1454-9. 2004
  9. pmc Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice
    Thomas A Lagace
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Invest 116:2995-3005. 2006
  10. pmc Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote
    Zhenze Zhao
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, TX 75390, USA
    Am J Hum Genet 79:514-23. 2006

Research Grants

  1. Targeting the serine protease PCSK9 via covalent complementarity
    John Chorba; Fiscal Year: 2013
  2. Zahid Ahmad; Fiscal Year: 2016
  3. Jingwen Liu; Fiscal Year: 2016
  4. An immunoadhesin for treatment of hypercholesterolemia
    KEITH WYCOFF; Fiscal Year: 2012
  5. Joseph L Goldstein; Fiscal Year: 2016
  6. Active Immunity Targeted at PCSK9 for the Treatment of Hypercholesterolemia
    Ba Bie Teng; Fiscal Year: 2012
  7. Sekar Kathiresan; Fiscal Year: 2015
  8. Sergio Fazio; Fiscal Year: 2014
  9. PCSK9-LDLR inhibitors from fragment-based design
    JOHN LAURENCE KULP; Fiscal Year: 2013
  10. Hyperinsulinemia, mTOR activity and plasma lipoproteins
    ALAN RICHARD TALL; Fiscal Year: 2012

Patents

  1. Nucleic acid molecules derived from rat brain and programmed cell death models
  2. Narc-1, novel subtilase-like homologs

Detail Information

Publications198 found, 100 shown here

  1. ncbi Sequence variations in PCSK9, low LDL, and protection against coronary heart disease
    Jonathan C Cohen
    Donald W Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    N Engl J Med 354:1264-72. 2006
    ..We examined the effect of DNA-sequence variations that reduce plasma levels of LDL cholesterol on the incidence of coronary events in a large population...
  2. ncbi Mutations in PCSK9 cause autosomal dominant hypercholesterolemia
    Marianne Abifadel
    INSERM U383, Hopital Necker Enfants Malades, AP HP, Universite Paris V, 149 161 Rue de Sèvres, 75743 Paris Cedex 15, France
    Nat Genet 34:154-6. 2003
    ..We mapped a third locus associated with ADH, HCHOLA3 at 1p32, and now report two mutations in the gene PCSK9 (encoding proprotein convertase subtilisin/kexin type 9) ..
  3. ncbi Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis
    Yue Wei Qian
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
    J Lipid Res 48:1488-98. 2007
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease that regulates low density lipoprotein receptor (LDLR) protein levels. The mechanisms of this action, however, remain to be defined...
  4. ncbi Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation
    Da Wei Zhang
    Department of Molecular Genetics, The Donald W Reynolds Cardiovascular Clinical Research Center, Howard Hughes Institute, University of Texas Southwestern Medical Center, Dallas 75390, USA
    J Biol Chem 282:18602-12. 2007
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of hepatic low density lipoprotein receptors (LDLR), the major route of clearance of circulating cholesterol...
  5. ncbi The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2
    Steve Poirier
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 283:2363-72. 2008
    The proprotein convertase PCSK9 gene is the third locus implicated in familial hypercholesterolemia, emphasizing its role in cardiovascular diseases...
  6. pmc A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol
    Ingrid K Kotowski
    McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, 75390 9046, USA
    Am J Hum Genet 78:410-22. 2006
    Selected missense mutations in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) cause autosomal dominant hypercholesterolemia, whereas nonsense mutations in the same gene are associated with low plasma ..
  7. pmc Effects of the prosegment and pH on the activity of PCSK9: evidence for additional processing events
    Suzanne Benjannet
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 285:40965-78. 2010
    b>PCSK9, a target for the treatment of dyslipidemia, enhances the degradation of the LDL receptor (LDLR) in endosomes/lysosomes, up-regulating LDL-cholesterol levels...
  8. ncbi Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia
    Geneviève Dubuc
    Laboratory of Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Quebec, Canada
    Arterioscler Thromb Vasc Biol 24:1454-9. 2004
    ..The NARC-1 gene, PCSK9, has been identified recently as the third locus implicated in autosomal dominant hypercholesterolemia (ADH)...
  9. pmc Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice
    Thomas A Lagace
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Invest 116:2995-3005. 2006
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a member of the proteinase K subfamily of subtilases that reduces the number of LDL receptors (LDLRs) in liver through an undefined posttranscriptional mechanism...
  10. pmc Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote
    Zhenze Zhao
    Department of Molecular Genetics, University of Texas Southwestern Medical Center at Dallas, TX 75390, USA
    Am J Hum Genet 79:514-23. 2006
    ..Mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) that are associated with lower plasma levels of LDL-C confer protection from coronary heart disease...
  11. ncbi The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR
    Nasha Nassoury
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7
    Traffic 8:718-32. 2007
    Mutations in the proprotein convertase PCSK9 gene are associated with autosomal dominant familial hyper- or hypocholesterolemia...
  12. pmc Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor
    Da Wei Zhang
    Department of Molecular Genetics, McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390 8591, USA
    Proc Natl Acad Sci U S A 105:13045-50. 2008
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that controls plasma LDL cholesterol levels by posttranslational regulation of the LDL receptor (LDLR)...
  13. pmc Hepatocyte nuclear factor 1alpha plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine
    Hai Li
    Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA
    J Biol Chem 284:28885-95. 2009
    b>PCSK9 is a natural inhibitor of LDL receptor (LDLR) that binds the extracellular domain of LDLR and triggers its intracellular degradation...
  14. pmc Elevated PCSK9 levels in untreated patients with heterozygous or homozygous familial hypercholesterolemia and the response to high-dose statin therapy
    Frederick Raal
    Carbohydrate and Lipid Metabolism Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa
    J Am Heart Assoc 2:e000028. 2013
    b>Proprotein convertase subtilisin kexin type 9 (PCSK9) is an enzyme that impairs low-density lipoprotein cholesterol (LDL-C) clearance from the plasma by promoting LDL receptor degradation...
  15. pmc Loss- and gain-of-function PCSK9 variants: cleavage specificity, dominant negative effects, and low density lipoprotein receptor (LDLR) degradation
    Suzanne Benjannet
    Laboratory of Biochemical Neuroendocrinology, University of Montreal, Montreal, Quebec, Canada
    J Biol Chem 287:33745-55. 2012
    The proprotein convertase PCSK9 is a major target in the treatment of hypercholesterolemia because of its ability bind the LDL receptor (LDLR) and enhance its degradation in endosomes/lysosomes...
  16. pmc Proprotein convertase subtilisin/kexin type 9 deficiency reduces melanoma metastasis in liver
    Xiaowei Sun
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, University of Montreal, Montreal, QC, Canada
    Neoplasia 14:1122-31. 2012
    ..The proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density lipoprotein cholesterol homeostasis by targeting the low-density lipoprotein receptor (LDLR)..
  17. pmc The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain
    Eric N Hampton
    Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 104:14604-9. 2007
    Mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) are strongly associated with levels of low-density lipoprotein cholesterol in the blood plasma and, thereby, occurrence or resistance to atherosclerosis and coronary ..
  18. pmc Longitudinal association of PCSK9 sequence variations with low-density lipoprotein cholesterol levels: the Coronary Artery Risk Development in Young Adults Study
    Chiang Ching Huang
    Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
    Circ Cardiovasc Genet 2:354-61. 2009
    Mutations of PCSK9 are associated cross-sectionally with plasma low-density lipoprotein cholesterol (LDL-C) levels, but little is known about their longitudinal association with LDL-C levels from young adulthood to middle age.
  19. pmc Molecular basis for LDL receptor recognition by PCSK9
    Hyock Joo Kwon
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 9050, USA
    Proc Natl Acad Sci U S A 105:1820-5. 2008
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) posttranslationally regulates hepatic low-density lipoprotein receptors (LDLRs) by binding to LDLRs on the cell surface, leading to their degradation...
  20. pmc A proprotein convertase subtilisin-like/kexin type 9 (PCSK9) C-terminal domain antibody antigen-binding fragment inhibits PCSK9 internalization and restores low density lipoprotein uptake
    Yan G Ni
    Department of Cardiovascular Diseases, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Biol Chem 285:12882-91. 2010
    b>PCSK9 binds to the low density lipoprotein receptor (LDLR) and leads to LDLR degradation and inhibition of plasma LDL cholesterol clearance...
  21. pmc Genetic and metabolic determinants of plasma PCSK9 levels
    Susan G Lakoski
    Donald W Reynolds Cardiovascular Clinical Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
    J Clin Endocrinol Metab 94:2537-43. 2009
    b>PCSK9 is a secreted protein that influences plasma levels of low-density lipoprotein cholesterol (LDL-C) and susceptibility to coronary heart disease...
  22. doi Structural and biochemical characterization of the wild type PCSK9-EGF(AB) complex and natural familial hypercholesterolemia mutants
    Matthew J Bottomley
    Department of Biochemistry, Istituto di Ricerca di Biologia Molecolare P Angeletti, Via Pontina Km 30 600, 00040 Pomezia Rome, Italy
    J Biol Chem 284:1313-23. 2009
    b>PCSK9 regulates low density lipoprotein receptor (LDLR) levels and consequently is a target for the prevention of atherosclerosis and coronary heart disease. Here we studied the interaction, of LDLR EGF(A/AB) repeats with PCSK9...
  23. doi Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women
    Lena Persson
    Metabolism Unit, Department of Endocrinology, Metabolism and Diabetes, Karolinska Institute at Karolinska University Hospital Huddinge S 141 86 Stockholm, Sweden
    Arterioscler Thromb Vasc Biol 32:810-4. 2012
    ..We evaluated how increased levels of endogenous estrogens modulate cholesterol and lipoprotein metabolism in women...
  24. pmc PCSK9 SNP rs11591147 is associated with low cholesterol levels but not with cognitive performance or noncardiovascular clinical events in an elderly population
    Iris Postmus
    Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
    J Lipid Res 54:561-6. 2013
    Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) is a protein involved in LDL-cholesterol metabolism...
  25. pmc Characterization of proprotein convertase subtilisin/kexin type 9 (PCSK9) trafficking reveals a novel lysosomal targeting mechanism via amyloid precursor-like protein 2 (APLP2)
    Rachel M DeVay
    Rinat Pfizer Inc, South San Francisco, California 94080, USA
    J Biol Chem 288:10805-18. 2013
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low density lipoprotein receptor protein levels by diverting it to lysosomes...
  26. doi Plasma PCSK9 is a late biomarker of severity in patients with severe trauma injury
    Maëlle Le Bras
    Institut National de la Santé et de la Recherche Médicale INSERM Unité Mixte de Recherche UMR 1087, University Hospital of Nantes, F 44000 Nantes, France
    J Clin Endocrinol Metab 98:E732-6. 2013
    PCSK9 (proprotein convertase subtilisin kexin type 9) is a secreted protease that modulates cholesterol homeostasis by decreasing low-density lipoprotein receptor expression...
  27. ncbi Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol
    William E Alborn
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA
    Clin Chem 53:1814-9. 2007
    b>Proprotein convertase subtilisin kexin type 9 (PCSK9) is gaining attention as a key regulator of serum LDL-cholesterol (LDLC). This novel serine protease causes the degradation of hepatic LDL receptors by an unknown mechanism...
  28. doi Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels
    Gaetan Mayer
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 283:31791-801. 2008
    The proprotein convertase subtilisin/kexin-type 9 (PCSK9), which promotes degradation of the hepatic low density lipoprotein receptor (LDLR), is now recognized as a major player in plasma cholesterol metabolism...
  29. doi Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans
    Lena Persson
    Department of Endocrinology, Center for Biosciences and Nutrition, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden
    Arterioscler Thromb Vasc Biol 30:2666-72. 2010
    To gain insight into the function of proprotein convertase subtilisin kexin type 9 (PCSK9) in humans by establishing whether circulating levels are influenced by diurnal, dietary, and hormonal changes.
  30. pmc PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain
    Mali Liu
    Neurology Department, Merck Research Laboratories, West Point, PA, USA
    J Lipid Res 51:2611-8. 2010
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that regulates hepatic low-density lipoprotein receptor (LDLR) levels in humans...
  31. pmc In vivo evidence that furin from hepatocytes inactivates PCSK9
    Rachid Essalmani
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 286:4257-63. 2011
    The proprotein convertase PCSK9 plays a key role in cholesterol homeostasis by binding the LDL receptor and targeting it toward degradation...
  32. pmc Novel domain interaction regulates secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein
    Fen Du
    Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, South Carolina 29209, USA
    J Biol Chem 286:43054-61. 2011
    b>PCSK9 (proprotein convertase subtilisin/kexin type 9) has emerged as a novel therapeutic target for hypercholesterolemia due to its LDL receptor (LDLR)-reducing activity...
  33. doi Association between plasma PCSK9 and gamma-glutamyl transferase levels in diabetic patients
    Bertrand Cariou
    INSERM, U915, Nantes F 44000, France
    Atherosclerosis 211:700-2. 2010
    b>Proprotein convertase subtilisin kexin type 9 (PCSK9) is a secreted proprotein convertase acting as a natural inhibitor of the low-density lipoprotein (LDL) receptor...
  34. ncbi Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia
    T P Leren
    Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet, Oslo, Norway
    Clin Genet 65:419-22. 2004
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is at a locus for autosomal dominant hypercholesterolemia, and recent data indicate that the PCSK9 gene is involved in cholesterol biosynthesis...
  35. pmc A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis
    Suet N Chen
    Section of Cardiology, Center for Preventive Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA
    J Am Coll Cardiol 45:1611-9. 2005
    We sought to determine the effects of PCSK9 variants on plasma low-density lipoprotein cholesterol (LDL-C) levels, severity of coronary atherosclerosis, and response to statin therapy in the Lipoprotein Coronary Atherosclerosis Study (..
  36. pmc The E670G SNP in the PCSK9 gene is associated with polygenic hypercholesterolemia in men but not in women
    David Evans
    Endokrinologie und Stoffwechsel, Medizinische Klinik III, Zentrum fur Innere Medizin, Universitatsklinikum Hamburg Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
    BMC Med Genet 7:66. 2006
    Common genetic variants in the PCSK9 gene have been reported to be associated with both elevated and exceptionally low LDL levels...
  37. ncbi Proapoptotic effects of NARC 1 (= PCSK9), the gene encoding a novel serine proteinase
    Brendan Bingham
    Neuroscience Discovery Research, Wyeth Research, Princeton, New Jersey 08543 8000, USA
    Cytometry A 69:1123-31. 2006
    b>NARC 1/PCSK9 encodes a novel serine proteinase known to play a role in cholesterol homeostasis. NARC 1 mRNA expression in cerebellar granule neurons (CGNs) was discovered to be induced following an apoptotic injury...
  38. ncbi Relation of PCSK9 mutations to serum low-density lipoprotein cholesterol in childhood and adulthood (from The Bogalusa Heart Study)
    D Michael Hallman
    Human Genetics Center, University of Texas Health Science Center, Houston, Texas, USA
    Am J Cardiol 100:69-72. 2007
    Specific mutations in the gene for proprotein convertase, subtilisin-kexin type 9 (PCSK9), that are associated with lower coronary heart disease risk may produce lifelong decreases in low-density lipoprotein (LDL) cholesterol levels, but ..
  39. pmc Proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is a risk factor of large-vessel atherosclerosis stroke
    Sherine Abboud
    Laboratory of Experimental Neurology, Department of Neurology, Erasme Hospital, Universite Libre de Bruxelles, Brussels, Belgium
    PLoS ONE 2:e1043. 2007
    Genetic variation in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been recently identified as an important determinant of plasma LDL-cholesterol and severity of coronary heart disease...
  40. doi Dual mechanisms for the fibrate-mediated repression of proprotein convertase subtilisin/kexin type 9
    Sanae Kourimate
    INSERM U915, CHU Hotel Dieu, 9 quai Moncousu, Nantes, France
    J Biol Chem 283:9666-73. 2008
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with familial autosomal dominant hypercholesterolemia and is a natural inhibitor of the LDL receptor (LDLr)...
  41. pmc Variation in PCSK9, low LDL cholesterol, and risk of peripheral arterial disease
    Aaron R Folsom
    Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55454, United States
    Atherosclerosis 202:211-5. 2009
    We hypothesized that variants in PCSK9 that lower LDL cholesterol levels are associated with reduced prevalence and incidence of peripheral artery disease (PAD).
  42. doi PCSK9 dominant negative mutant results in increased LDL catabolic rate and familial hypobetalipoproteinemia
    Bertrand Cariou
    INSERM, U915, Nantes F 44000, France
    Arterioscler Thromb Vasc Biol 29:2191-7. 2009
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a central player in the regulation of cholesterol homeostasis, increasing the low-density lipoprotein (LDL) receptor degradation...
  43. pmc The multifaceted proprotein convertases: their unique, redundant, complementary, and opposite functions
    Nabil G Seidah
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal IRCM, affiliated with the University of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 288:21473-81. 2013
    ..convertase (PC) family comprises nine members: PC1/3, PC2, furin, PC4, PC5/6, PACE4, PC7, SKI-1/S1P, and PCSK9. The first seven PCs cleave their substrates at single or paired basic residues, and SKI-1/S1P cleaves its ..
  44. ncbi The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population
    Amanda J Hooper
    Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia
    Atherosclerosis 193:445-8. 2007
    Missense mutations in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) can cause familial hypercholesterolemia...
  45. doi Mutations and polymorphisms in the proprotein convertase subtilisin kexin 9 (PCSK9) gene in cholesterol metabolism and disease
    Marianne Abifadel
    Institut Nationale de la Santé et de la Recherche Médicale INSERM, U781, Paris, France
    Hum Mutat 30:520-9. 2009
    ..Our discovery in 2003 of the first mutations of the proprotein convertase subtilisin kexin 9 gene (PCSK9) causing ADH shed light on an unknown actor in cholesterol metabolism that since then has been extensively ..
  46. doi A chimeric LDL receptor containing the cytoplasmic domain of the transferrin receptor is degraded by PCSK9
    Øystein L Holla
    Medical Genetics Laboratory, Department of Medical Genetics, Oslo University Hospital Rikshospitalet, NO 0027 Oslo, Norway
    Mol Genet Metab 99:149-56. 2010
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the extracellular domain of the low density lipoprotein receptor (LDLR) at the cell surface, and disrupts the normal recycling of the LDLR...
  47. ncbi The PCSK9 gene R46L variant is associated with lower plasma lipid levels and cardiovascular risk in healthy U.K. men
    Marileia Scartezini
    Department of Medical Pathology, Federal University of Parana, Rua Lothário Meissner 3400, Curitiba Paraná 80210 170, Brazil
    Clin Sci (Lond) 113:435-41. 2007
    In the present study, we have determined the relative frequency of the R46L, I474V and E670G variants in the PCSK9 (protein convertase subtilisin/kexin type 9) gene and its association with plasma lipid levels and CHD (coronary heart ..
  48. doi PCSK9 binds to multiple receptors and can be functionally inhibited by an EGF-A peptide
    LiXin Shan
    Department of Cardiovascular and Metabolic Disease Research, Schering Plough Research Institute, 2015 Galloping Hill Road, K 15 1 1945, Kenilworth, NJ 07033, USA
    Biochem Biophys Res Commun 375:69-73. 2008
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low density lipoprotein receptor (LDLR) and induces its internalization and degradation...
  49. ncbi Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9
    Jonathan Cohen
    Donald W Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines, Dallas, Texas 75390 9046, USA
    Nat Genet 37:161-5. 2005
    ..Missense mutations in PCSK9, encoding a serine protease in the secretory pathway, also cause hypercholesterolemia...
  50. doi Proprotein convertase subtilisin/kexin type 9 interacts with apolipoprotein B and prevents its intracellular degradation, irrespective of the low-density lipoprotein receptor
    Hua Sun
    University of Texas Graduate School of Biomedical Sciences at Houston, USA
    Arterioscler Thromb Vasc Biol 32:1585-95. 2012
    proprotein convertase subtilisin/kexin type 9 (PCSK9) negatively regulates the low-density lipoprotein (LDL) receptor (LDLR) in hepatocytes and therefore plays an important role in controlling circulating levels of LDL-cholesterol...
  51. ncbi Plasma PCSK9 levels correlate with cholesterol in men but not in women
    Janice Mayne
    Hormones, Growth and Development Program, Ottawa Health Research Institute, The Ottawa Hospital, University of Ottawa, Ottawa, Ont, Canada
    Biochem Biophys Res Commun 361:451-6. 2007
    Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that negatively regulates low density lipoprotein receptor (LDLR) levels...
  52. ncbi The regulated cell surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substrates
    Gaetan Mayer
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 283:2373-84. 2008
    ..of PC5A is enhanced, as evidenced by the cleavage of the PC5A substrates Lefty, ADAMTS-4, endothelial lipase, and PCSK9. Our data suggest a novel mechanism for PC5A activation and substrate cleavage at the cell surface, through a ..
  53. doi Secreted proprotein convertase subtilisin/kexin type 9 reduces both hepatic and extrahepatic low-density lipoprotein receptors in vivo
    Robert J Schmidt
    Lilly Research Laboratories, Eli Lilly and Company, Cardiovascular Research, 355 Merrill Street, Indianapolis, IN 46285, USA
    Biochem Biophys Res Commun 370:634-40. 2008
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that is known to reduce hepatic low-density lipoprotein receptor (LDLR) levels and increase plasma LDL cholesterol...
  54. ncbi Evidence for effect of mutant PCSK9 on apolipoprotein B secretion as the cause of unusually severe dominant hypercholesterolaemia
    Xi Ming Sun
    MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK
    Hum Mol Genet 14:1161-9. 2005
    ..or apolipoprotein B genes that result in defective clearance of plasma LDL by the liver, but a third gene (PCSK9), encoding a putative proprotein convertase, has recently been implicated...
  55. ncbi Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia
    Delphine Allard
    INSERM UR383, Hopital Necker Enfants Malades
    Hum Mutat 26:497. 2005
    ..We previously demonstrated that ADH is also caused by mutations of the PCSK9 (proprotein convertase subtilisin/kexin type 9) gene that encodes Narc-1 (neural apoptosis-regulated convertase 1)...
  56. pmc The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation
    Nabil G Seidah
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, H2W 1R7 Canada
    Proc Natl Acad Sci U S A 100:928-33. 2003
    ..5 telencephalon cells led to enhanced recruitment of undifferentiated neural progenitor cells into the neuronal lineage, suggesting that NARC-1 is implicated in the differentiation of cortical neurons...
  57. ncbi Functional characterization of Narc 1, a novel proteinase related to proteinase K
    Saule Naureckiene
    Neuroscience Discovery Research, Wyeth Research, CN 8000, Princeton, NJ 08543 8000, USA
    Arch Biochem Biophys 420:55-67. 2003
    The NARC 1 gene encodes a novel proteinase K family proteinase...
  58. ncbi Genetic variants in PCSK9 affect the cholesterol level in Japanese
    Keisuke Shioji
    Department of Epidemiology, Research Institute, National Cardiovascular Center, 5 7 1 Fujishirodai Suita, Osaka 565 8565, Japan
    J Hum Genet 49:109-14. 2004
    Mutations in the proprotein convertase subtilisin/kexin 9 ( PCSK9) gene have been reported in affected members of two families with autosomal dominant hypercholesterolemia...
  59. ncbi A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree
    Kirsten M Timms
    Myriad Genetics, Salt Lake City, UT 84108, USA
    Hum Genet 114:349-53. 2004
    ..This variant results in a D374Y missense change in the gene PCSK9.
  60. ncbi Apolipoprotein B100 metabolism in autosomal-dominant hypercholesterolemia related to mutations in PCSK9
    Khadija Ouguerram
    INSERM U 539, Centre de Recherche en Nutrition Humaine de Nantes, France
    Arterioscler Thromb Vasc Biol 24:1448-53. 2004
    ..FH) related to mutation in proprotein convertase subtilisin/kexin type 9 (PCSK9) gene previously named neural apoptosis regulated convertase 1 (Narc-1). Our aim was to define the metabolic bases of this new form of hypercholesterolemia.
  61. ncbi NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol
    Suzanne Benjannet
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 279:48865-75. 2004
    The discovery of autosomal dominant hypercholesterolemic patients with mutations in the PCSK9 gene, encoding the proprotein convertase NARC-1, resulting in the missense mutations suggested a role in low density lipoprotein (LDL) ..
  62. ncbi Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cells
    Florent Lalanne
    Institut National de la Santé et de la Recherche Médicale U539, Centre Hospitalier Universitaire, Hotel Dieu, Nantes, France
    J Lipid Res 46:1312-9. 2005
    Mutations in Proprotein Convertase Subtilisin Kexin 9 (PCSK9) have been associated with autosomal dominant hypercholesterolemia...
  63. ncbi Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: long-term follow-up and treatment response
    Rossi P Naoumova
    MRC Clinical Sciences Centre, Hammersmith Hospital, London W12 0NN, UK
    Arterioscler Thromb Vasc Biol 25:2654-60. 2005
    ..of long-term (30 years) clinical history and response to treatment of 13 patients with the D374Y mutation of PCSK9 (PCSK9 patients) from 4 unrelated white British families compared with 36 white British patients with heterozygous ..
  64. ncbi Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c
    Philippe Costet
    INSERM, U539, CHU Hotel Dieu, 44000, Nantes, France
    J Biol Chem 281:6211-8. 2006
    ..Mutations in a third gene, proprotein convertase subtilisin kexin 9 (PCSK9), were recently associated to this disease...
  65. ncbi The c.43_44insCTG variation in PCSK9 is associated with low plasma LDL-cholesterol in a Caucasian population
    Pin Yue
    Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri, USA
    Hum Mutat 27:460-6. 2006
    ..Recently, loss-of-function mutations of PCSK9 gene have been shown to be associated with the hypocholesterolemia phenotype...
  66. ncbi The proprotein convertase (PC) PCSK9 is inactivated by furin and/or PC5/6A: functional consequences of natural mutations and post-translational modifications
    Suzanne Benjannet
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 281:30561-72. 2006
    b>PCSK9 is the ninth member of the proprotein convertase (PC) family. Some of its natural mutations have been genetically associated with the development of a dominant form of familial hyper- or hypocholesterolemia...
  67. ncbi [PCSK9, from gene to protein: a new actor involved in cholesterol homeostasis]
    Marianne Abifadel
    INSERM U781, AP HP, Hopital Necker Enfants Malades, 149, rue de Sevres, 75743 Paris, France
    Med Sci (Paris) 22:916-8. 2006
  68. pmc Genetic causes of familial hypercholesterolaemia in patients in the UK: relation to plasma lipid levels and coronary heart disease risk
    S E Humphries
    J Med Genet 43:943-9. 2006
    ..the relative frequency of mutations in three different genes (low-density lipoprotein receptor (LDLR), APOB, PCSK9), and to examine their effect in development of coronary heart disease (CHD) in patients with clinically defined ..
  69. ncbi A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol
    Tommaso Fasano
    Department of Biomedical Sciences, University of Modena and Reggio Emilia, Via Campi 287, I 41100 Modena, Italy
    Arterioscler Thromb Vasc Biol 27:677-81. 2007
    The PCSK9 gene, encoding a pro-protein convertase involved in posttranslational degradation of low-density lipoprotein receptor, has emerged as a key regulator of plasma low-density lipoprotein cholesterol...
  70. ncbi Genetic variants in PCSK9 in the Japanese population: rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population
    Yasuko Miyake
    Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, 5 7 1 Fujishirodai, Suita, Osaka 565 8565, Japan
    Atherosclerosis 196:29-36. 2008
    ..lipoprotein cholesterol (LDL-C) levels in the general population are influenced by rare sequence variations in the PCSK9 gene...
  71. ncbi The proprotein convertases are potential targets in the treatment of dyslipidemia
    Nabil G Seidah
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal, Quebec, H2W 1R7, Canada
    J Mol Med (Berl) 85:685-96. 2007
    ..furin, PC4, PC5/6, PACE4 and PC7, and two other PCs, SKI-1 (subtilisin-kexin isozyme-1)/S1P (site-1 protease) and PCSK9 (proprotein convertase subtilisin kexin 9) that cleave at nonbasic residues...
  72. ncbi Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia
    David Cunningham
    Pfizer Inc, Eastern Point Road, Groton, Connecticut 06430, USA
    Nat Struct Mol Biol 14:413-9. 2007
    b>Proprotein convertase subtilisin kexin type 9 (PCSK9) lowers the abundance of surface low-density lipoprotein (LDL) receptor through an undefined mechanism...
  73. ncbi The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol
    Derek E Piper
    Department of Molecular Structure, Amgen Inc, 1120 Veterans Boulevard, South San Francisco, California 94080, USA
    Structure 15:545-52. 2007
    b>Proprotein convertase subtilisin kexin type 9 (PCSK9) has been shown to be involved in the regulation of extracellular levels of the low-density lipoprotien receptor (LDLR)...
  74. ncbi Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells
    Markey C McNutt
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 282:20799-803. 2007
    Proprotein convertase subtilisin/kexin type 9 (PCSK9), a member of the proteinase K subfamily of subtilases, promotes internalization and degradation of low density lipoprotein receptors (LDLRs) after binding the receptor on the surface ..
  75. pmc Self-association of human PCSK9 correlates with its LDLR-degrading activity
    Daping Fan
    Atherosclerosis Research Unit, Division of Cardiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232 6300, USA
    Biochemistry 47:1631-9. 2008
    Genetic studies have demonstrated an important role for proprotein convertase subtilisin/kexin type 9 (PCSK9) as a determinant of plasma cholesterol levels. However, the underlying molecular mechanism is not completely understood...
  76. doi Genetic variation at the PCSK9 locus moderately lowers low-density lipoprotein cholesterol levels, but does not significantly lower vascular disease risk in an elderly population
    Eliana Polisecki
    Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA
    Atherosclerosis 200:95-101. 2008
    Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (..
  77. doi Characterization of novel mutations in the catalytic domain of the PCSK9 gene
    J Cameron
    Department of Medical Genetics, Medical Genetics Laboratory, Rigshospitalet Radiumhospitalet Medical Centre, Oslo, Norway
    J Intern Med 263:420-31. 2008
    To expand our understanding of the structure and function of proprotein convertase subtilisin/kexin type 9 (PCSK9) by studying how naturally occurring mutations in PCSK9 disrupt the function of PCSK9.
  78. doi PCSK9: an enigmatic protease
    Dayami Lopez
    Department of Experimental Therapeutics, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
    Biochim Biophys Acta 1781:184-91. 2008
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in cholesterol metabolism by controlling the levels of low density lipoprotein (LDL) particles that circulate in the bloodstream...
  79. doi The activation and physiological functions of the proprotein convertases
    Nabil G Seidah
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada
    Int J Biochem Cell Biol 40:1111-25. 2008
    ..The two other convertases SKI-1/S1P and PCSK9 are implicated in cholesterol and/or fatty acid metabolism...
  80. doi Polymorphisms associated with cholesterol and risk of cardiovascular events
    Sekar Kathiresan
    Cardiovascular Disease Prevention Center, Cardiology Division, Massachusetts General Hospital, MA 02114, USA
    N Engl J Med 358:1240-9. 2008
    ..We tested the hypothesis that a combination of such SNPs contributes to the risk of cardiovascular disease...
  81. doi Berberine decreases PCSK9 expression in HepG2 cells
    Jamie Cameron
    Medical Genetics Laboratory, Department of Medical Genetics, Rikshospitalet University Hospital, Oslo, Norway
    Atherosclerosis 201:266-73. 2008
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) post-transcriptionally downregulates the low-density lipoprotein receptor (LDLR) by binding to the receptor's epidermal growth factor repeat A on the cell surface and shuttling the ..
  82. doi A PCSK9 missense variant associated with a reduced risk of early-onset myocardial infarction
    Sekar Kathiresan
    N Engl J Med 358:2299-300. 2008
  83. doi Molecular basis of PCSK9 function
    Gilles Lambert
    The Heart Research Institute, Camperdown, NSW 2050, Australia
    Atherosclerosis 203:1-7. 2009
    The LDL receptor (LDLr) inhibitor Proprotein Convertase Subtilisin Kexin type 9 (PCSK9) has emerged as a genetically validated target for lowering plasma LDL cholesterol levels...
  84. pmc Function and distribution of circulating human PCSK9 expressed extrahepatically in transgenic mice
    Yi Luo
    Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research and Development, Groton New London Laboratories, Groton, CT 06340, USA zer com
    J Lipid Res 50:1581-8. 2009
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is predominantly expressed in liver and regulates cholesterol metabolism by down regulating liver LDL receptor (LDLR) proteins...
  85. doi The PCSK9 gene E670G polymorphism affects low-density lipoprotein cholesterol levels but is not a risk factor for coronary artery disease in ethnic Chinese in Taiwan
    Lung An Hsu
    Department of Internal Medicine, Chang Gung University College of Medicine, Taipei, Taiwan
    Clin Chem Lab Med 47:154-8. 2009
    An E670G polymorphism of the exon 12 of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene was recently found to be associated with increased plasma low-density lipoprotein cholesterol (LDL-C) levels and severity of coronary ..
  86. pmc Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor
    Christopher J Duff
    Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, U K
    Biochem J 419:577-84. 2009
    b>PCSK9 (proprotein convertase subtilisin/kexin type 9) promotes degradation of the LDLR [LDL (low-density lipoprotein) receptor] through an as-yet-undefined mechanism, leading to a reduction in cellular LDLc (LDL-cholesterol) and a ..
  87. pmc Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants
    Sekar Kathiresan
    Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Nat Genet 41:334-41. 2009
    ..observations (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9)...
  88. pmc Antagonism of secreted PCSK9 increases low density lipoprotein receptor expression in HepG2 cells
    Markey C McNutt
    Departments of Molecular Genetics, Biochemistry, and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 284:10561-70. 2009
    b>PCSK9 is a secreted protein that degrades low density lipoprotein receptors (LDLRs) in liver by binding to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR...
  89. doi Effects of PCSK9 variants on common carotid artery intima media thickness and relation to ApoE alleles
    Giuseppe Danilo Norata
    Department of Pharmacological Sciences, Universita degli Studi di Milano, Via Balzaretti 9, Milan, Italy
    Atherosclerosis 208:177-82. 2010
    b>PCSK9 plays a key role in plasma cholesterol metabolism by modulating the expression of LDL receptors.
  90. pmc Dissection of the endogenous cellular pathways of PCSK9-induced low density lipoprotein receptor degradation: evidence for an intracellular route
    Steve Poirier
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 284:28856-64. 2009
    ..in at least three major genes, the LDL receptor (LDLR), its ligand apolipoprotein B, and the proprotein convertase PCSK9. Single point mutations in PCSK9 are associated with either hyper- or hypocholesterolemia...
  91. doi Healthy individuals carrying the PCSK9 p.R46L variant and familial hypercholesterolemia patients carrying PCSK9 p.D374Y exhibit lower plasma concentrations of PCSK9
    Steve E Humphries
    Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, The Royal Free and University College London Medical School, London, UK
    Clin Chem 55:2153-61. 2009
    We measured plasma PCSK9 concentrations in healthy men with a PCSK9 (proprotein convertase subtilisin/kexin type 9) loss-of-function variant (p...
  92. doi Comprehensive whole-genome and candidate gene analysis for response to statin therapy in the Treating to New Targets (TNT) cohort
    John F Thompson
    Helicos BioSciences, Cambridge, MA, USA
    Circ Cardiovasc Genet 2:173-81. 2009
    ..To address this, 5745 individuals from the Treating to New Targets (TNT) trial were genotyped in a combination of a whole-genome and candidate gene approach to identify associations with response to atorvastatin treatment...
  93. doi Mutation detection rate and spectrum in familial hypercholesterolaemia patients in the UK pilot cascade project
    A Taylor
    Great Ormond Street Hospital for Children, London, UK
    Clin Genet 77:572-80. 2010
    ..Arg3527Gln and PCSK9 p.Asp374Tyr using a commercial amplification refractory mutation system (ARMS) kit...
  94. doi Increased secretion of lipoproteins in transgenic mice expressing human D374Y PCSK9 under physiological genetic control
    Bronwen Herbert
    Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, DuCane Road, London W12 0NN, England
    Arterioscler Thromb Vasc Biol 30:1333-9. 2010
    To produce transgenic mice expressing the D374Y variant of the human proprotein convertase subtilisin/kexin type 9 (PCSK9) gene at physiological levels to investigate the mechanisms causing hypercholesterolemia and accelerated ..
  95. pmc A locked nucleic acid antisense oligonucleotide (LNA) silences PCSK9 and enhances LDLR expression in vitro and in vivo
    Nidhi Gupta
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada
    PLoS ONE 5:e10682. 2010
    The proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important factor in the etiology of familial hypercholesterolemia (FH) and is also an attractive therapeutic target to reduce low density lipoprotein (LDL) cholesterol...
  96. doi PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease: 3 independent studies and meta-analyses
    Marianne Benn
    Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
    J Am Coll Cardiol 55:2833-42. 2010
    The aim of this study was to examine the effect of PCSK9 R46L on low-density lipoprotein cholesterol (LDL-C), risk of ischemic heart disease (IHD), and mortality.
  97. doi Plasma PCSK9 is increased by fenofibrate and atorvastatin in a non-additive fashion in diabetic patients
    P Costet
    INSERM, U915, Nantes F 44000, France
    Atherosclerosis 212:246-51. 2010
    Proprotein convertase subtilisin kexin/type 9 (PCSK9) is an inhibitor of the low density (LDL) lipoprotein receptor. Plasma PCSK9 is increased by fenofibrate and statins...
  98. pmc Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9 and cholesterol biosynthesis in humans
    Jeffrey D Browning
    Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
    J Lipid Res 51:3359-63. 2010
    Proprotein convertase, subtilisin/kexin type 9 (PCSK9), a key regulator of plasma LDL-cholesterol (LDL-c) and cardiovascular risk, is produced in liver and secreted into plasma where it binds hepatic LDL receptors (LDLR), leading to ..
  99. pmc A two-step binding model of PCSK9 interaction with the low density lipoprotein receptor
    Taichi Yamamoto
    Center for Prevention of Obesity, Cardiovascular Disease and Diabetes, Children s Hospital Oakland Research Institute, Oakland, California 94609, USA
    J Biol Chem 286:5464-70. 2011
    b>PCSK9 (proprotein convertase subtilisin-like/kexin type 9) is an emerging target for pharmaceutical intervention. This multidomain protein interacts with the LDL receptor (LDLR), promoting receptor degradation...
  100. doi Removal of acidic residues of the prodomain of PCSK9 increases its activity towards the LDL receptor
    Øystein L Holla
    Unit for Cardiac and Cardiovascular Genetics, Department of Medical Genetics, Oslo, Norway
    Biochem Biophys Res Commun 406:234-8. 2011
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) at the cell surface and mediates intracellular degradation of the LDLR...
  101. pmc Role of the C-terminal domain of PCSK9 in degradation of the LDL receptors
    Øystein L Holla
    Unit for Cardiac and Cardiovascular Genetics, Department of Medical Genetics, Centre for Molecular Biology and Neuroscience, University of Oslo, Oslo, Norway
    J Lipid Res 52:1787-94. 2011
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) at the cell surface and disrupts the normal recycling of the LDLR...

Research Grants44

  1. Targeting the serine protease PCSK9 via covalent complementarity
    John Chorba; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease which regulates LDL cholesterol levels and, by extension, the development of atherosclerosis...
  2. Zahid Ahmad; Fiscal Year: 2016
    ..LDL receptor (LDLR), apolipoprotein B-100 (APOB), and proprotein convertase subtilisin-like kexin type 9 (PCSK9)...
  3. Jingwen Liu; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): PCSK9 (proprotein convertase subtilisin/kexin type 9) plays an important role in the control of circulating LDL- cholesterol (LDL-C) levels via modulation of rates of degradation of hepatic LDL ..
  4. An immunoadhesin for treatment of hypercholesterolemia
    KEITH WYCOFF; Fiscal Year: 2012
    ..Proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein secreted in the liver, plays a key role in maintaining cholesterol homeostasis by regulating cell-..
  5. Joseph L Goldstein; Fiscal Year: 2016
    ..SREBP processing, thereby determining LDL receptor number and plasma LDL level;2) discovery of mutations in PCSK9 that lower plasma LDL and decrease heart attacks as much as 88%;3) demonstration that PCSK9 functions ..
  6. Active Immunity Targeted at PCSK9 for the Treatment of Hypercholesterolemia
    Ba Bie Teng; Fiscal Year: 2012
    ..applicant): The long-term objective of this proposal is to design and develop novel strategies to inhibit/reduce PCSK9 action...
  7. Sekar Kathiresan; Fiscal Year: 2015
    ..We will only study families where known causes of FHBL (e.g., APOB and PCSK9) have been ruled out;(2) To perform sequencing of the exome in 2-4 affected individuals from each of 10 families ..
  8. Sergio Fazio; Fiscal Year: 2014
    DESCRIPTION (provided by applicant): Proprotein convertase subtilisin kexin type 9 (PCSK9) regulates plasma cholesterol levels by enhancing the intracellular degradation of the LDL receptor (LDLR), the primary driver of LDL clearance ..
  9. PCSK9-LDLR inhibitors from fragment-based design
    JOHN LAURENCE KULP; Fiscal Year: 2013
    ..phase II clinical studies demonstrate that an antibody targeting proportion convertase subtilisin/kexin type 9 (PCSK9)-a target for the treatment of hypercholesterolemia and coronary heart disease-successfully and safely decreases ..
  10. Hyperinsulinemia, mTOR activity and plasma lipoproteins
    ALAN RICHARD TALL; Fiscal Year: 2012
    ..of LDLR appear to be regulated by a distinctive pathway downstream of mTOR that leads to decreased expression of Pcsk9 and a post-transcriptional increase in LDLR...
  11. LAURIE HOLLIS GLIMCHER; Fiscal Year: 2014
    ..Our recent discovery that XBP1 directly regulates the expression of PCSK9 may partly explain its effect on serum cholesterol...
  12. Novel Modulators of LDL Metabolism
    Nabil Elshourbagy; Fiscal Year: 2009
    ..Our therapeutic target is the interface between the protease proprotein convertase subtilisin-like kexin type 9 (PCSK9) and the low density lipoprotein receptor (LDLR), where we propose to identify and develop compounds that prevent ..
  13. Theranostic nanoparticles to enhance morpholino delivery to the liver for suppres
    DAVID PETER CORMODE; Fiscal Year: 2011
    ..Two approaches for reducing cholesterol production will be attempted: 1) PCSK9 knockdown and 2) miR-122 suppression...
  14. Lipid genotypes, phenotypes, and colorectal adenomas: Elucidating mechanisms
    Polly A Newcomb; Fiscal Year: 2013
    ..associations between genetic loci known to influence lipid levels and the risk of colorectal neoplasia, including PCSK9, ABCG8, and APOE, but these studies have been limited to only a few candidate genes...
  15. DAVID PETER CORMODE; Fiscal Year: 2014
    ..Two approaches for reducing cholesterol production will be attempted: 1) PCSK9 knockdown and 2) miR-122 suppression...
  16. MARK IAN MCCARTHY; Fiscal Year: 2015
    ..by observing LoF variants that provide protection against disease without undesirable consequences (as in CCR5 and PCSK9)...
  17. Low-Pass Sequencing and High-Density SNP Genotyping for Type 2 Diabetes
    MICHAEL LEE contact BOEHNKE; Fiscal Year: 2010
    ..in particular, by querying lower-frequency causal alleles (such as those found in IL23R, NOD2, IFIH1, and PCSK9)...
  18. Proprotein Processing, Trafficking and Secretion Gordon Conference
    Nabil Seidah; Fiscal Year: 2006
    ..The integration of protease systems that are required both for normal physiology and human disease will be relevant to our understanding of the molecular bases of diabetes, cancer, Alzheimer's and drug addiction. ..
  19. GENETIC DETERMINANTS OF PLASMA LIPOPROTEINS
    Jonathan Cohen; Fiscal Year: 2002
    ..These studies will help to determine the role of variation in hepatic lipase activity in determining plasma HDL concentrations, and LDL size distribution, two important risk factors for coronary artery disease. ..
  20. Taskforce for Obesity Research at Southwestern (RMI)
    JAY HORTON; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  21. Pathogenesis of Obesity and Metabolic Syndrome
    JAY HORTON; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  22. Characterization of Microsomal Fatty Acid Elongation
    JAY HORTON; Fiscal Year: 2007
    ..abstract_text> ..
  23. PHYTOESTROGEN REGULATION OF BONE TURNOVER
    HARRY BLAIR; Fiscal Year: 2004
    ..Thus, through a systematic and logically set series of experiments, the principal investigator proposes to clarify a role for phytoestrogens in bone cell regulation. ..
  24. CALMODULIN AND CGMP CONTROL OF OSTEOCLASTIC H+ SECRETION
    HARRY BLAIR; Fiscal Year: 2003
    ..This knowledge will be useful in understanding how osteoporosis develops, and may assist in the design of treatments to reduce bone resorption and prevent osteoporosis. ..
  25. Regulation of Osteoclast Activity by Calcium and cGMP
    Harry C Blair; Fiscal Year: 2010
    ..The mechanisms defined by these studies will highlight potential targets for pharmacological intervention in osteoporosis. ..
  26. Identifying Kidney Disease Genes Through Mutagenesis
    RONNY KORSTANJE; Fiscal Year: 2009
    ....
  27. THROMBOTIC, INFLAMMATORY & GENE MARKERS OF CVD IN WOMEN
    Paul Ridker; Fiscal Year: 2002
    ....
  28. SECONDARY PREVENTION TRIAL OF VENOUS THROMBOSIS
    Paul Ridker; Fiscal Year: 2002
    ....
  29. RECEPTOR-MEDIATED ENDOCYTOSIS--MECHANISM AND FUNCTION
    FREDERICK MAXFIELD; Fiscal Year: 2004
    ..These studies will lead to an increasingly complete description of endocytic trafficking pathways. ..
  30. Structure and Function of the LDL Receptor
    STEPHEN BLACKLOW; Fiscal Year: 2006
    ..Determine how the ligand-binding modules of the LDL receptor recognize apolipoprotein E (apoE)-containing ligands. 2. Elucidate the mechanism of ligand release by the LDLR at low pH. ..
  31. INTERACTIONS BETWEEN MICROGLIA AND BETA AMYLOID PLAQUES
    FREDERICK MAXFIELD; Fiscal Year: 2004
    ..We will analyze the mechanisms of degradation of AB amyloid in microglia and also determine whether soluble AB peptides become incorporated into insoluble AB in the endosomes and lysosomes of microglia. ..
  32. Pilot Study of Pancreas Cancer & Diabetes Genes in CARET
    Melissa Austin; Fiscal Year: 2006
    ..The results may facilitate translational studies of early detection and prevention of pancreatic cancer, especially among patients diagnosed with diabetes. [unreadable] [unreadable]..
  33. Regulation of Tangential Migration in the Embryonic CNS
    Andrew Peterson; Fiscal Year: 2004
    ..abstract_text> ..
  34. DEFECTIVE FOREBRAIN DEVELOPMENT IN MUTANT MICE
    Andrew Peterson; Fiscal Year: 2002
    ..The genetics of the phenotype will be studied by using linkage analysis to map the mutations. ..
  35. CYSTOLIC-FREE CALCIUM AND CELL MOTILITY
    FREDERICK MAXFIELD; Fiscal Year: 2003
    ..Finally, the role of myosin and of oriented recycling will be examined in neutrophils migrating through endothelial cell monolayers and through natural biological matrices, which resemble the physiological sites of neutrophil function. ..
  36. GENETIC EPIDEMIOLOGY OF CHANGE IN CVD RISK FACTORS
    DAVID MICHAEL HALLMAN; Fiscal Year: 2010
    ....
  37. GENETICS OF THE METABOLIC SYNDROME IN JAPANESE AMERICANS
    Melissa Austin; Fiscal Year: 2002
    ....
  38. Structure and Function in Notch Signaling
    STEPHEN BLACKLOW; Fiscal Year: 2008
    ..Aim 3. Investigate the functional implications of Notch dimerization in models of differentiation and disease pathogenesis. ..
  39. Osteoprotegerin Pathway: Relations of Genes & Biomarkers to CVD in the Community
    Sekar Kathiresan; Fiscal Year: 2008
    ..In addition, the candidate will be well positioned to transition from conducting pathway-based investigation to genome-wide association studies for cardiovascular phenotypes. [unreadable] [unreadable]..
  40. Oncogenic Notch Signaling: Structural Studies
    STEPHEN BLACKLOW; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  41. Genotypes, Haplotypes, and Blood Pressure Change from Childhood to Adulthood
    DAVID MICHAEL HALLMAN; Fiscal Year: 2010
    ....
  42. Genes, Hormomes, Growth, and Body Fat: Project HeartBeat
    DAVID MICHAEL HALLMAN; Fiscal Year: 2010
    ..Our analyses may also help identify genetic variants that may predispose some individuals toward obesity. ..

Patents2

  1. Nucleic acid molecules derived from rat brain and programmed cell death models
    Patent Number: WO0131007-A2; Date:2001-05-03
  2. Narc-1, novel subtilase-like homologs
    Patent Number: WO0157081-A2; Date:2001-08-09