PCSK9

Summary

Gene Symbol: PCSK9
Description: proprotein convertase subtilisin/kexin type 9
Alias: FH3, HCHOLA3, LDLCQ1, NARC-1, NARC1, PC9, 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. 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
  7. 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
  8. 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
  9. 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
  10. 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

Detail Information

Publications174 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. 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...
  7. 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 ..
  8. 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...
  9. 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...
  10. 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) ..
  11. 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
    Proprotein convertase subtilisin kexin type 9 (PCSK9) lowers the abundance of surface low-density lipoprotein (LDL) receptor through an undefined mechanism...
  12. 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)...
  13. 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...
  14. pmc Mechanistic implications for LDL receptor degradation from the PCSK9/LDLR structure at neutral pH
    Paola Lo Surdo
    Department of Biochemistry and Molecular Biology, IRBM P Angeletti, Via Pontina Km 30 600, Pomezia, Rome I 00040, Italy
    EMBO Rep 12:1300-5. 2011
    The protein PCSK9 (proprotein convertase subtilisin/kexin type 9) is a key regulator of low-density lipoprotein receptor (LDLR) levels and cardiovascular health...
  15. 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...
  16. 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...
  17. 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)...
  18. 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...
  19. 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)..
  20. 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...
  21. 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...
  22. 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 ..
  23. 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...
  24. 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.
  25. 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.
  26. 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
    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)...
  27. 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...
  28. 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...
  29. 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 ..
  30. 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 ..
  31. 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...
  32. 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 (..
  33. 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...
  34. pmc The M2 module of the Cys-His-rich domain (CHRD) of PCSK9 protein is needed for the extracellular low-density lipoprotein receptor (LDLR) degradation pathway
    Yascara Grisel Luna Saavedra
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, IRCM, affiliated to the University of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 287:43492-501. 2012
    b>PCSK9 enhances the cellular degradation of the LDL receptor (LDLR), leading to increased plasma LDL cholesterol...
  35. 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...
  36. 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...
  37. 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...
  38. 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...
  39. 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...
  40. 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...
  41. 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...
  42. 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...
  43. 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...
  44. 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
    Proprotein convertase subtilisin kexin type 9 (PCSK9) is a secreted proprotein convertase acting as a natural inhibitor of the low-density lipoprotein (LDL) receptor...
  45. 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 ..
  46. 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...
  47. 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.
  48. 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 ..
  49. 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...
  50. 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...
  51. 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.
  52. 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 (..
  53. 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 ..
  54. pmc Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation
    Nabil G Seidah
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Affiliated to the Université de Montréal, Montreal, Quebec, Canada
    PLoS ONE 7:e41865. 2012
    Proprotein convertase subtilisin/kexin-9 (PCSK9) enhances the degradation of hepatic low-density lipoprotein receptor (LDLR)...
  55. 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 ..
  56. 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...
  57. 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.
  58. 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...
  59. 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...
  60. pmc Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR
    Yan Wang
    Department of Molecular Genetics, Howard Hughes Medical Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    J Lipid Res 53:1932-43. 2012
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that promotes degradation of cell surface LDL receptors (LDLRs) in selected cell types...
  61. 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 ..
  62. 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...
  63. 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...
  64. 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
    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...
  65. 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...
  66. 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...
  67. 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...
  68. 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...
  69. 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...
  70. 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 ..
  71. 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...
  72. 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...
  73. 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...
  74. 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.
  75. 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...
  76. 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...
  77. 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 ..
  78. 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...
  79. 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)...
  80. 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...
  81. ncbi Effect of mutations in the PCSK9 gene on the cell surface LDL receptors
    Jamie Cameron
    Medical Genetics Laboratory, Department of Meical Genetics, Rikshospitalet University Hospital, N 0027 Oslo, Norway
    Hum Mol Genet 15:1551-8. 2006
    The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is involved in the post-transcriptional regulation of the low-density lipoprotein (LDL) receptors (LDLR)...
  82. 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...
  83. 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)...
  84. ncbi Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia
    Livia Pisciotta
    Department of Internal Medicine, University of Genoa, Viale Benedetto XV 6, I 16132 Genoa, Italy
    Atherosclerosis 186:433-40. 2006
    ..coronary disease (pCAD) than simple heterozygotes for mutations in either these genes or for missense mutations in PCSK9 gene. It is not known whether combined mutations in LDLR and PKCS9 are associated with such a severe phenotype...
  85. ncbi Effects of ezetimibe and/or simvastatin on LDL receptor protein expression and on LDL receptor and HMG-CoA reductase gene expression: a randomized trial in healthy men
    Ioanna Gouni-Berthold
    Department of Internal Medicine II, University of Cologne, Kerpener Street 62, 50937 Cologne, Germany
    Atherosclerosis 198:198-207. 2008
    ..The molecular mechanisms underlying the pronounced lipid-lowering effects of this combination have not been fully elucidated in humans...
  86. doi Rare genetic causes of autosomal dominant or recessive hypercholesterolaemia
    Anne K Soutar
    Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, London W12 0NN, UK
    IUBMB Life 62:125-31. 2010
    ..More recently, defects in two other genes, LDLRAP1 and PCSK9, have been found in patients with FH and investigation of these has shed new light on the functioning and ..
  87. ncbi Portuguese Familial Hypercholesterolemia Study: presentation of the study and preliminary results
    Mafalda Bourbon
    Unidade de Investigação Cardiovascular, Centro de Biopatologia, Instituto Nacional de Saude Dr Ricardo Jorge, Lisboa, Portugal
    Rev Port Cardiol 25:999-1013. 2006
    ..In 1999 the Portuguese Familial Hypercholesterolemia Study was begun at the National Institute of Health...
  88. pmc Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and Apolipoprotein B among 6382 white women in genome-wide analysis with replication
    Daniel I Chasman
    Center for Cardiovascular Disease Prevention, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02215, USA
    Circ Cardiovasc Genet 1:21-30. 2008
    ....
  89. pmc A mutation in Tac1p, a transcription factor regulating CDR1 and CDR2, is coupled with loss of heterozygosity at chromosome 5 to mediate antifungal resistance in Candida albicans
    Alix Coste
    Institute of Microbiology, University Hospital Lausanne, Switzerland
    Genetics 172:2139-56. 2006
    ..of matched azole-susceptible (DSY294; FH1: heterozygous at mating-type locus) and azole-resistant isolates (DSY296; FH3: homozygous at mating-type locus)...
  90. pmc A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa
    Francisco Rivero
    Center for Biochemistry and Center for Molecular Medicine, Medical Faculty, University of Cologne, Joseph Stelzmann Strasse 52, 50931 Koln, Germany
    BMC Genomics 6:28. 2005
    ..Formins act as profilin-modulated processive actin nucleators conserved throughout a wide range of eukaryotes...
  91. 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...
  92. pmc Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment
    Kara N Maxwell
    Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 102:2069-74. 2005
    Proprotein convertase subtilisin kexin 9 (PCSK9) is a member of the subtilisin serine protease family with an important role in cholesterol metabolism...
  93. ncbi Implication of the proprotein convertase NARC-1/PCSK9 in the development of the nervous system
    Steve Poirier
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada
    J Neurochem 98:838-50. 2006
    Neural apoptosis-regulated convertase-1/proprotein convertase subtilisin-kexin like-9 (NARC-1/PCSK9) is a proprotein convertase recently described to play a major role in cholesterol homeostasis through enhanced degradation of the low-..
  94. doi EhNCABP166: a nucleocytoplasmic actin-binding protein from Entamoeba histolytica
    A D Campos-Parra
    Departamento de Biomedicina Molecular, Centro de Investigacion y de Estudios, Avanzados del I P N 2508, Col San Pedro Zacatenco, 07360 Mexico, D F, Mexico
    Mol Biochem Parasitol 172:19-30. 2010
    ..Two (Bin1/Amphiphysin/Rvs167) (BAR) domains, one GTPase-binding/formin 3 homology (GBD/FH3) domain, three Bcl2-associated athanogene (BAG) domains, one basic-leucine zipper (bZIP) domain and one poly(A)-..
  95. ncbi Localization of a mammalian homolog of diaphanous, mDia1, to the mitotic spindle in HeLa cells
    T Kato
    Department of Pharmacology, Kyoto University Faculty of Medicine, Sakyo, Kyoto 606 8501, Japan
    J Cell Sci 114:775-84. 2001
    ..It is a member of the formin homology (FH) proteins and contains the Rho-binding domain and an FH3 region in its N terminus, an FH1 region containing polyproline stretches in the middle and an FH2 region in the C ..
  96. ncbi Complete genomes of two Human hepatitis A virus isolates from China: analysis and comparison with other isolates
    Y Hu
    Department of Vaccine Research, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union of Medical College, 379 Jiaoling Road, Kunming, 650118 Yunnan, P R China
    Acta Virol 46:153-7. 2002
    ..LU38 and LY6 from China were determined and compared with those of wt HHAV isolates AH1, AH2, AH3, FH1, FH2, FH3, GBM, HM175, LA and MBB...
  97. ncbi Inhibition of squalene synthase upregulates PCSK9 expression in rat liver
    Mohini Bedi
    Department of Molecular Medicine, School of Basic Biomedical Sciences, University of South Florida, College of Medicine, Tampa, FL 33612, USA
    Arch Biochem Biophys 470:116-9. 2008
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in cholesterol metabolism by enhancing the degradation of the LDL receptor protein in the liver...
  98. ncbi Mutational heterogeneity in low-density lipoprotein receptor gene related to familial hypercholesterolemia in Morocco
    R Chater
    Laboratoire de Biochimie, Groupe de Génétique et Biologie Moléculaire, Faculte des Sciences Ain Chock, BP 5366 Maarif, Casablanca, Morocco
    Clin Chim Acta 373:62-9. 2006
    ..lipoprotein receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Until now, molecular data concerning FH in Morocco is still limited...
  99. ncbi Bile acids and lipoprotein metabolism: effects of cholestyramine and chenodeoxycholic acid on human hepatic mRNA expression
    L M Nilsson
    Department of Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden
    Biochem Biophys Res Commun 357:707-11. 2007
    ..the expression of the LDL receptor (LDLR) by about 65% and that of proprotein convertase subtilisin kexin 9 (PCSK9) by 70%...
  100. doi Moderate phenotypic expression of familial hypercholesterolemia in Tunisia
    Awatef Jelassi
    Research Unit of Genetic and Biological Factors of Atherosclerosis, Faculty of Medicine, Monastir, Tunisia
    Clin Chim Acta 411:735-8. 2010
    ..density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes...
  101. ncbi Molecular diagnosis of hypobetalipoproteinemia: an ENID review
    Patrizia Tarugi
    Department of Biomedical Sciences, University of Modena e Reggio Emilia, Via Campi 287, I 41100 Modena, Italy
    Atherosclerosis 195:e19-27. 2007
    ..Recently a FHBL plasma lipid phenotype was observed in carriers of mutations of the PCSK9 gene causing loss of function of the encoded protein, a proprotein convertase which regulates LDL-receptor number ..

Research Grants96

  1. Genetic Determinants of Coronary Atherosclerosis
    Jonathan C Cohen; Fiscal Year: 2010
    ..The second locus encodes the proprotein convertase PCSK9 which is associated with decreased levels of LDL-C and substantial protection against incident CHD in the ARIC ..
  2. Fatty Acid Synthesis in Specific Hypothalamic Neurons: Control of Appetite and En
    Joseph Goldstein; Fiscal Year: 2007
    ..and selective 25-hydroxyvitamin D deficiency (vitamin D 25-hydroxylase); 7) use of knockout mice to show that PCSK9 is a major regulator of LDLR protein levels in liver; and 8) development of the nonsynonymous codon approach to ..
  3. From Sugar to Fat: How the Transcription Factor XBP1 Regulates Hepatic Lipogenesi
    LAURIE HOLLIS GLIMCHER; Fiscal Year: 2010
    ..Our recent discovery that XBP1 directly regulates the expression of PCSK9 may partly explain its effect on serum cholesterol...
  4. 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. ..
  5. Genetic Determinants of Coronary Atherosclerosis
    Jonathan Cohen; Fiscal Year: 2007
    ..The second locus encodes the proprotein convertase PCSK9 which is associated with decreased levels of LDL-C and substantial protection against incident CHD in the ARIC ..
  6. Taskforce for Obesity Research at Southwestern (RMI)
    JAY HORTON; Fiscal Year: 2006
    ....
  7. Cardiovascular Disease Epidemiology & Prevention Trng
    Aaron Folsom; Fiscal Year: 2007
    ..The continued need for qualified cardiovascular epidemiologists and the program's documented success justify its continuance. ..
  8. Characterization of Microsomal Fatty Acid Elongation
    JAY HORTON; Fiscal Year: 2007
    ..abstract_text> ..
  9. DIET, HDL, AND REVERSE CHOLESTEROL TRANSPORT
    JAY HORTON; Fiscal Year: 2003
    ..abstract_text> ..
  10. Pathogenesis of Obesity and Metabolic Syndrome
    JAY HORTON; Fiscal Year: 2006
    ....
  11. Regulation of Tangential Migration in the Embryonic CNS
    Andrew Peterson; Fiscal Year: 2004
    ..abstract_text> ..
  12. 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. ..
  13. 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. ..
  14. GENETIC EPIDEMIOLOGY OF HYPERTRIGLYCERIDEMIA
    Melissa Austin; Fiscal Year: 1993
    ....
  15. DEFECTIVE FOREBRAIN DEVELOPMENT IN MUTANT MICE
    Andrew Peterson; Fiscal Year: 2004
    ..Finally we will examine the known and predicted protein associates of the RERE gene product to determine the proximal effects of its loss ..
  16. 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. ..
  17. FOLDING AND BINDING DETERMINANTS OF THE LDL RECEPTOR
    STEPHEN BLACKLOW; Fiscal Year: 2001
    ..Eventually, small molecules may be identified which suppress the folding defects in some of the FH mutations, and which might serve as therapeutics for patients with FH. ..
  18. Macrophage-lipoprotein interactions
    Frederick R Maxfield; Fiscal Year: 2010
    ..Research findings based on these studies may lead to new treatments to prevent or reverse the formation of atherosclerotic lesions. ..
  19. GENETIC EPIDEMIOLOGY OF CHANGE IN CVD RISK FACTORS
    DAVID MICHAEL HALLMAN; Fiscal Year: 2010
    ....
  20. Structure and Function in Notch Signaling
    STEPHEN BLACKLOW; Fiscal Year: 2009
    ....
  21. Non-Alcoholic Fatty Liver Disease Ethnicity and Hepatic Metabolism
    Jeffrey Browning; Fiscal Year: 2007
    ..e., obesity, diabetes, metabolic syndrome). Therefore, a second objective of this research will be to define ethnic differences in hepatic metabolism and relate these differences to the risk of developing hepatic steatosis. ..
  22. Genes, Hormomes, Growth, and Body Fat: Project HeartBeat
    DAVID HALLMAN; Fiscal Year: 2007
    ..Our analyses may also help identify genetic variants that may predispose some individuals toward obesity. ..
  23. GENETICS OF THE METABOLIC SYNDROME IN JAPANESE AMERICANS
    Melissa Austin; Fiscal Year: 2002
    ....
  24. Oncogenic Notch Signaling: Structural Studies
    STEPHEN BLACKLOW; Fiscal Year: 2006
    ....
  25. GENETIC EPIDEMIOLOGY OF CHANGE IN CVD RISK FACTORS
    DAVID HALLMAN; Fiscal Year: 2004
    ..The proposed research promises to extend our knowledge of the genetic factors affecting the course of CVD risk factor development over a substantial portion of an individual's lifetime. ..
  26. GENETIC EPIDEMIOLOGY OF CHANGE IN CVD RISK FACTORS
    DAVID HALLMAN; Fiscal Year: 2007
    ....
  27. Genotypes, Haplotypes, and Blood Pressure Change from Childhood to Adulthood
    DAVID HALLMAN; Fiscal Year: 2009
    ....
  28. Osteoprotegerin Pathway: Relations of Genes & Biomarkers to CVD in the Community
    Sekar Kathiresan; Fiscal Year: 2007
    ..In addition, the candidate will be well positioned to transition from conducting pathway-based investigation to genome-wide association studies for cardiovascular phenotypes. ..
  29. 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. ..
  30. Genotypes, Haplotypes, and Blood Pressure Change from Childhood to Adulthood
    DAVID MICHAEL HALLMAN; Fiscal Year: 2010
    ....