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 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
  4. 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
  5. 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
  6. 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
  7. ncbi 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
  8. 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
  9. 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
  10. ncbi 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

Research Grants

  1. Fatty Acid Synthesis in Specific Hypothalamic Neurons: Control of Appetite and En
    Joseph Goldstein; Fiscal Year: 2007
  2. From Sugar to Fat: How the Transcription Factor XBP1 Regulates Hepatic Lipogenesi
    LAURIE HOLLIS GLIMCHER; Fiscal Year: 2010
  3. Proprotein Processing, Trafficking and Secretion Gordon Conference
    Nabil Seidah; Fiscal Year: 2006
  4. Genetic Determinants of Coronary Atherosclerosis
    Jonathan C Cohen; Fiscal Year: 2010
  5. Genetic Determinants of Coronary Atherosclerosis
    Jonathan Cohen; Fiscal Year: 2007
  6. DIET, HDL, AND REVERSE CHOLESTEROL TRANSPORT
    JAY HORTON; Fiscal Year: 2003
  7. Cardiovascular Disease Epidemiology & Prevention Trng
    Aaron Folsom; Fiscal Year: 2007
  8. Characterization of Microsomal Fatty Acid Elongation
    JAY HORTON; Fiscal Year: 2007
  9. Taskforce for Obesity Research at Southwestern (RMI)
    JAY HORTON; Fiscal Year: 2006
  10. Pathogenesis of Obesity and Metabolic Syndrome
    JAY HORTON; Fiscal Year: 2006

Detail Information

Publications149 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 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...
  4. 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...
  5. 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...
  6. 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...
  7. ncbi 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...
  8. 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)...
  9. 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 ..
  10. ncbi 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)...
  11. ncbi 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...
  12. 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...
  13. ncbi 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 ..
  14. ncbi 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 ..
  15. 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)...
  16. ncbi 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...
  17. 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...
  18. ncbi 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...
  19. 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...
  20. ncbi 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...
  21. 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...
  22. ncbi 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...
  23. 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...
  24. 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...
  25. ncbi 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...
  26. 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)...
  27. 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.
  28. 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...
  29. 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...
  30. 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...
  31. 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)...
  32. 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) ..
  33. ncbi 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...
  34. ncbi 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...
  35. ncbi 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...
  36. 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 ..
  37. 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...
  38. ncbi 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)...
  39. 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...
  40. 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.
  41. 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...
  42. ncbi 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...
  43. ncbi 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 (..
  44. 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...
  45. 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...
  46. 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...
  47. 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...
  48. ncbi 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 ..
  49. 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...
  50. ncbi 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
    ....
  51. ncbi 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)...
  52. ncbi 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...
  53. ncbi 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...
  54. ncbi 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...
  55. 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-..
  56. ncbi 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)-..
  57. 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 ..
  58. 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...
  59. 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%...
  60. 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...
  61. 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...
  62. 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 ..
  63. ncbi Biochemical characterization of the diaphanous autoregulatory interaction in the formin homology protein FHOD1
    André Schönichen
    Max Planck Institute for Molecular Physiology, Department of Physical Biochemistry, D 44227 Dortmund, Germany
    J Biol Chem 281:5084-93. 2006
    ..Importantly, the FH3 domain of FHOD1 does not overlap with the proposed Rac1-binding domain...
  64. ncbi 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...
  65. ncbi Knock-out mouse models of proprotein convertases: unique functions or redundancy?
    John W M Creemers
    Laboratory of Biochemical Neuroendocrinology, Center for Human Genetics K U Leuven, Belgium
    Front Biosci 13:4960-71. 2008
    ..of precursors within hydrophobic residues performed by the convertase S1P/SKI-1 and the convertase NARC-1/PCSK9 seems to prefer cleavages at the motif LVFAQSIP...
  66. ncbi PCSK9 impedes hepatitis C virus infection in vitro and modulates liver CD81 expression
    Patrick Labonte
    Institut Armand Frappier, Institut National de Recherche Scientifique, Laval, Quebec, Canada
    Hepatology 50:17-24. 2009
    Human PCSK9 is known to enhance the degradation of membrane-bound receptors such as the hepatocyte low-density lipoprotein receptor (LDLR), ApoER2, and very low-density lipoprotein receptor...
  67. ncbi Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2
    Hyun Jeong Jeong
    Department of Biochemistry, Kwandong University College of Medicine, Kangnung, Kangwon do 210 701, Korea
    J Lipid Res 49:399-409. 2008
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a member of the subtilases that promotes the internalization and degradation of LDL receptor in liver and thereby controls the level of LDL cholesterol in plasma...
  68. ncbi Cellular and secreted pro-protein convertase subtilisin/kexin type 9 catalytic activity in hepatocytes
    Sanae Kourimate
    INSERM, U915, Nantes, France
    Atherosclerosis 206:134-40. 2009
    Pro-protein convertase subtilisin/kexin type 9 (PCSK9) impairs the low density lipoprotein receptor (LDLr) recyling. To reach the LDLr, the pro-protein must cleave itself in the endoplasmic reticulum...
  69. ncbi New hypotheses about the structure-function of proprotein convertase subtilisin/kexin type 9: analysis of the epidermal growth factor-like repeat A docking site using WaterMap
    Robert A Pearlstein
    Novartis Institutes for BioMedical Research, Global Discovery Chemistry, Cambridge, Massachusetts 02139, USA
    Proteins 78:2571-86. 2010
    ..LDL-R is targeted for lysosomal degradation by association with proprotein convertase subtilisin-kexin type 9 (PCSK9). Gain of function mutations in PCSK9 can result in excessive loss of receptors and dyslipidemia...
  70. ncbi Proprotein convertase subtilisin/kexin type 9 (PCSK9): hepatocyte-specific low-density lipoprotein receptor degradation and critical role in mouse liver regeneration
    Ahmed Zaid
    Laboratorie of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, affiliated to the University of Montreal, Montreal, Quebec, Canada
    Hepatology 48:646-54. 2008
    The gene encoding the proprotein convertase subtilisin/kexin type 9 (PCSK9) is linked to familial hypercholesterolemia, as are those of the low-density lipoprotein receptor (LDLR) and apolipoprotein B...
  71. ncbi Proprotein convertase subtilisin/kexin type 9 (PCSK9) affects gene expression pathways beyond cholesterol metabolism in liver cells
    Hong Lan
    Cardiovascular and Metabolic Disease Research, Merck Research Laboratories, Kenilworth, New Jersey 0703, USA
    J Cell Physiol 224:273-81. 2010
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) induces degradation of low-density lipoprotein receptor (LDLR) in the liver. It is being pursued as a therapeutic target for LDL-cholesterol reduction...
  72. ncbi 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...
  73. ncbi Fenofibrate treatment increases human serum proprotein convertase subtilisin kexin type 9 levels
    Jason S Troutt
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
    J Lipid Res 51:345-51. 2010
    Over the past several years, proprotein convertase subtilisin kexin type 9 (PCSK9) has gained significant attention as a key regulator of serum LDL-cholesterol (LDL-C) levels...
  74. ncbi 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 ..
  75. ncbi The multiple-wing-hairs gene encodes a novel GBD-FH3 domain-containing protein that functions both prior to and after wing hair initiation
    Jie Yan
    Biology Department, Department of Cell Biology, Morphogenesis and Regenerative Medicine Institute and Cancer Center, University of Virginia, Charlottesville, Virginia 22903, USA
    Genetics 180:219-28. 2008
    ..We identified mwh as CG13913, which encodes a novel G protein binding domain-formin homology 3 (GBD-FH3) domain protein. The Mwh protein accumulated on the proximal side of wing cells prior to hair formation...
  76. ncbi Transcriptional profiling reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver
    Linda M Sanderson
    Nutrigenomics Consortium, TI Food and Nutrition, Wageningen, The Netherlands
    Physiol Genomics 41:42-52. 2010
    ..Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARbeta/delta target genes...
  77. ncbi Importance of proprotein convertase subtilisin/kexin type 9 in the hormonal and dietary regulation of rat liver low-density lipoprotein receptors
    Lena Persson
    Department of Endocrinology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
    Endocrinology 150:1140-6. 2009
    ..here tested whether such observations may be due to regulation of proprotein convertase subtilisin/kexin type 9 (PCSK9)...
  78. ncbi LDLR and ApoB are major genetic causes of autosomal dominant hypercholesterolemia in a Taiwanese population
    Kai Chien Yang
    Division of Cardiology, Department of Internal Medicine, E Da Hospital, Kaohsiung, Taiwan
    J Formos Med Assoc 106:799-807. 2007
    ..lipoprotein receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9)...
  79. ncbi Limited mutational heterogeneity in the LDLR gene in familial hypercholesterolemia in Tunisia
    A Jelassi
    Research Unit of Genetic and Biologic Factors of Atherosclerosis, Faculty of Medecine, Monastir, Tunisia
    Atherosclerosis 203:449-53. 2009
    ..lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. In previous studies, we have identified novel mutations in Tunisian FH families...
  80. ncbi No genetic linkage or molecular evidence for involvement of the PCSK9, ARH or CYP7A1 genes in the Familial Hypercholesterolemia phenotype in a sample of Danish families without pathogenic mutations in the LDL receptor and apoB genes
    Dorte Damgaard
    Department of Medicine and Cardiology, Aarhus Sygehus, Aarhus University Hospital, Tage Hansens Gade 2, DK 8000 Aarhus C, Denmark
    Atherosclerosis 177:415-22. 2004
    ..analysis without being able to demonstrate mutations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene, the main candidate gene in the third FH locus...
  81. ncbi Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9
    Holly E Careskey
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
    J Lipid Res 49:394-8. 2008
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) has gained attention as a key regulator of serum low density lipoprotein cholesterol (LDL-C) levels...
  82. ncbi Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip
    Philippa J Talmud
    Centre for Cardiovascular Genetics, Department of Medicine, University College London, London WC1E 6JF, UK
    Am J Hum Genet 85:628-42. 2009
    ..SNPs associated with LDL cholesterol and apolipoprotein B were located in LDLR, PCSK9, APOB, CELSR2, HMGCR, CETP, the TOMM40-APOE-C1-C2-C4 cluster, and the APOA5-A4-C3-A1 cluster; SNPs associated with ..
  83. ncbi A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates
    Joyce C Y Chan
    Department of Metabolic Disorders, Amgen Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 106:9820-5. 2009
    Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) by interacting with the LDL receptor (LDLR) and is an attractive therapeutic target for LDL-C lowering...
  84. ncbi ForC, a novel type of formin family protein lacking an FH1 domain, is involved in multicellular development in Dictyostelium discoideum
    Chikako Kitayama
    Japan Society for the Promotion of Science, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305 8562, Japan
    J Cell Sci 116:711-23. 2003
    ..are highly conserved regulators of cytoskeletal organization and share three regions of homology: the FH1, FH2 and FH3 domains...
  85. ncbi Mechanisms of disease: genetic causes of familial hypercholesterolemia
    Anne K Soutar
    Lipoprotein Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK
    Nat Clin Pract Cardiovasc Med 4:214-25. 2007
    ..to the database of genes in which defects cause FH is one encoding a member of the proprotein convertase family, PCSK9. Rare dominant gain-of-function mutations in PCSK9 cosegregate with hypercholesterolemia, and one mutation is ..
  86. ncbi Rho1 has multiple functions in Drosophila wing planar polarity
    Jie Yan
    Biology Department, Department of Cell Biology, Morphogenesis and Regenerative Medicine Institute and Cancer Center, University of Virginia, Charlottesville, VA 22903, USA
    Dev Biol 333:186-99. 2009
    ..The existence of a G Protein Binding-Formin Homology 3 (GBD-FH3) domain in Multiple Wing Hairs, a downstream component of the pathway suggested that Rho1 might function by binding ..
  87. ncbi Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based lysine acetyltransferases post-translationally regulate BACE1 levels
    Mi Hee Ko
    Department of Medicine, University of Wisconsin Madison and Geriatric Research Education Clinical Center, Veterans Affairs Medical Center, Madison, Wisconsin 53705, USA
    J Biol Chem 284:2482-92. 2009
    ..The acetylation protects the nascent protein from degradation by PCSK9/NARC-1 in the ERGIC and allows it to reach the Golgi apparatus...
  88. ncbi The influence of PCSK9 polymorphisms on serum low-density lipoprotein cholesterol and risk of atherosclerosis
    Jean Davignon
    Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal IRCM, 110 Pine Avenue West, Montreal, QC, H2W 1R7, Canada
    Curr Atheroscler Rep 12:308-15. 2010
    Pro-protein-convertase-subtilisin-kexin-9 (PCSK9) enhances the degradation of the low-density lipoprotein receptor (LDLR) that plays a major role in cholesterol homeostasis...
  89. ncbi Chronic alcohol consumption disrupted cholesterol homeostasis in rats: down-regulation of low-density lipoprotein receptor and enhancement of cholesterol biosynthesis pathway in the liver
    Zhigang Wang
    Department of Human Nutrition, University of Illinois at Chicago, Illinois 60612, USA
    Alcohol Clin Exp Res 34:471-8. 2010
    ....
  90. ncbi [Familial hypercholesterolemia in Tunisia]
    A Jelassi
    Unité de recherche sur les facteurs génétiques et biologiques de l athérosclérose, Laboratoire de Biochimie, Faculte de medecine de Monastir, 5019 Monastir, Tunisie
    Pathol Biol (Paris) 57:444-50. 2009
    ..by a loss of function in the LDL receptor gene, or by a mutation in the gene encoding apolipoprotein B (APOB) or PCSK9 gene. In Tunisia, the frequency of this disease is about one of 165 for heterozygote...
  91. ncbi Roots of angiosperm formins: the evolutionary history of plant FH2 domain-containing proteins
    Michal Grunt
    Department of Plant Physiology, Faculty of Sciences, Charles University, Vinièná 5, CZ 128 43 Praha 2, Czech Republic
    BMC Evol Biol 8:115. 2008
    ....
  92. ncbi Intestinal and hepatic cholesterol carriers in diabetic Psammomys obesus
    Emile Levy
    Gastroenterology, Hepatology, and Nutrition Unit, Research Centre, Sainte Justine Hospital, 3175 Sainte Catherine Road, Montreal, Quebec, Canada
    Endocrinology 151:958-70. 2010
    ..Furthermore, jejunal PCSK9 protein was diminished and low-density lipoprotein receptor was raised, along with a significant down-regulation ..
  93. ncbi The proprotein convertases and their implication in sterol and/or lipid metabolism
    Nabil G Seidah
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal H2W 1R7, QC, Canada
    Biol Chem 387:871-7. 2006
    ..PC4, PC5/6, PACE4 and PC7, and two other subtilases that cleave at non-basic residues, called SKI-1/S1P and NARC-1/PCSK9. The present review concentrates on the regulatory role played by some of these convertases in cholesterol and ..
  94. ncbi Hepatic proprotein convertases modulate HDL metabolism
    Weijun Jin
    Department of Pharmacology, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell Metab 6:129-36. 2007
    ..show that inhibition in the liver of the classical proprotein convertases (PCs), but not the atypical PCs S1P and PCSK9, decreases plasma HDL-C levels...
  95. ncbi PCSK9 as a therapeutic target of dyslipidemia
    Nabil G Seidah
    Clinical Research Institute of Montreal, Laboratory of Biochemical Neuroendocrinology, 110 Pine Ave West, Montreal, QC, H2W 1R7 Canada
    Expert Opin Ther Targets 13:19-28. 2009
    Proprotein convertase subtilisin/kexin type 9 (PCSK9), which promotes degradation of hepatic low density lipoprotein receptor (LDLR), has a role in plasma cholesterol metabolism...
  96. ncbi Inflammation stimulates the expression of PCSK9
    Kenneth R Feingold
    Metabolism Section 111F, Department of Veterans Affairs Medical Center, 4150 Clement Street, University of California San Francisco, San Francisco, CA 94121, USA
    Biochem Biophys Res Commun 374:341-4. 2008
    Inflammation induces marked changes in lipid and lipoprotein metabolism. Proprotein convertase subtilisin kexin 9 (PCSK9) plays an important role in regulating LDL receptor degradation...
  97. ncbi Pseudoxanthoma elasticum and familial hypercholesterolemia: a deleterious combination of cardiovascular risk factors
    Livia Pisciotta
    Department of Internal Medicine, University of Genoa, I 16132 Genoa, Italy
    Atherosclerosis 210:173-6. 2010
    ..We investigated a 60-year-old female with angina pectoris found to have PXE, associated with elevated plasma LDL-C suspected to be due to autosomal-co-dominant hypercholesterolemia...
  98. ncbi Age-induced hypercholesterolemia in the rat relates to reduced elimination but not increased intestinal absorption of cholesterol
    Cecilia Gälman
    Karolinska Institute at Center for Endocrinology, Metabolism, and Diabetes, Department of Medicine and Molecular Nutrition Unit, Center for Nutrition and Toxicology, Novum, Karolinska University Hospital, Huddinge, Stockholm, Sweden
    Am J Physiol Endocrinol Metab 293:E737-42. 2007
    ..LDLRs), scavenger receptor class B type 1, and proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) transcripts were unchanged in old animals. GH treatment induced LDLRs, PCSK9 transcripts, and BA synthesis...
  99. ncbi Activation of the farnesoid X receptor represses PCSK9 expression in human hepatocytes
    Cédric Langhi
    INSERM, U915, CHU Hotel Dieu, Nord, Nantes F 44000, France
    FEBS Lett 582:949-55. 2008
    ..this study was to determine whether bile acids (BAs) modulate hepatic pro-protein convertase subtilisin/kexin 9 (PCSK9) gene expression. Immortalized human hepatocytes were treated with various BAs...
  100. ncbi Molecular pathways and agents for lowering LDL-cholesterol in addition to statins
    Philippe Costet
    INSERM, U915, Nantes, F 44000 France
    Pharmacol Ther 126:263-78. 2010
    ..ACAT), Acyl-CoA:diacylglycerol acyltransferases 2 (DGAT2), proprotein convertase subtilisin kexin type 9 (PCSK9)), and nuclear receptors (farnesoid X receptor (FXR), thyroid hormone receptor (TR)) that constitute interesting ..
  101. ncbi Cord blood lipoproteins and prenatal influences
    Narinder Bansal
    Clinical Epidemiology and Cardiovascular Medicine Group, Division of Cardiovascular and Endocrine Science, University Department of Medicine, Manchester Royal Infirmary, UK
    Curr Opin Lipidol 16:400-8. 2005
    ..Genetic and environmental influences affect cord blood lipoproteins, but how this occurs and the relative contribution of these influences to the overall profile in healthy newborns remains uncertain...

Research Grants78

  1. 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 ..
  2. 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...
  3. 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. ..
  4. 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 ..
  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. DIET, HDL, AND REVERSE CHOLESTEROL TRANSPORT
    JAY HORTON; Fiscal Year: 2003
    ..abstract_text> ..
  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. Taskforce for Obesity Research at Southwestern (RMI)
    JAY HORTON; Fiscal Year: 2006
    ....
  10. Pathogenesis of Obesity and Metabolic Syndrome
    JAY HORTON; Fiscal Year: 2006
    ....
  11. 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 ..
  12. 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. ..
  13. GENETIC EPIDEMIOLOGY OF HYPERTRIGLYCERIDEMIA
    Melissa Austin; Fiscal Year: 1993
    ....
  14. GENETIC EPIDEMIOLOGY OF CHANGE IN CVD RISK FACTORS
    DAVID MICHAEL HALLMAN; Fiscal Year: 2010
    ....
  15. 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. ..
  16. Structure and Function in Notch Signaling
    STEPHEN BLACKLOW; Fiscal Year: 2009
    ....
  17. 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. ..
  18. GENETICS OF THE METABOLIC SYNDROME IN JAPANESE AMERICANS
    Melissa Austin; Fiscal Year: 2002
    ....
  19. 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. ..
  20. 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. ..
  21. Oncogenic Notch Signaling: Structural Studies
    STEPHEN BLACKLOW; Fiscal Year: 2006
    ....
  22. Genotypes, Haplotypes, and Blood Pressure Change from Childhood to Adulthood
    DAVID MICHAEL HALLMAN; Fiscal Year: 2010
    ....
  23. 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. ..
  24. 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. ..
  25. Genotypes, Haplotypes, and Blood Pressure Change from Childhood to Adulthood
    DAVID HALLMAN; Fiscal Year: 2009
    ....
  26. GENETIC EPIDEMIOLOGY OF CHANGE IN CVD RISK FACTORS
    DAVID HALLMAN; Fiscal Year: 2007
    ....
  27. 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. ..