proprotein convertases

Summary

Summary: Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES.

Top Publications

  1. ncbi The biology and therapeutic targeting of the proprotein convertases
    Nabil G Seidah
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal affiliated to University of Montreal, 110 Pine Ave West, Montreal, Quebec H2W 1R7, Canada
    Nat Rev Drug Discov 11:367-83. 2012
  2. 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
  3. ncbi ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs
    J Ye
    Department of Molecular Genetics, University of Texas, Southwestern Medical Center, Dallas, TX 75390, USA
    Mol Cell 6:1355-64. 2000
  4. 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
  5. 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
  6. ncbi Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibiti
    Frederick Raal
    Carbohydrate and Lipid Metabolism Research Unit, Division of Endocrinology and Metabolism, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa
    Circulation 126:2408-17. 2012
  7. ncbi Effect of a monoclonal antibody to PCSK9 on LDL cholesterol
    Evan A Stein
    Metabolic and Atherosclerosis Research Center, 4685 Forest Ave, Cincinnati, OH 45212, USA
    N Engl J Med 366:1108-18. 2012
  8. 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
  9. pmc Increasing serum half-life and extending cholesterol lowering in vivo by engineering antibody with pH-sensitive binding to PCSK9
    Javier Chaparro-Riggers
    Rinat Pfizer Inc, South San Francisco, California 94080, USA
    J Biol Chem 287:11090-7. 2012
  10. 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

Research Grants

Detail Information

Publications267 found, 100 shown here

  1. ncbi The biology and therapeutic targeting of the proprotein convertases
    Nabil G Seidah
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal affiliated to University of Montreal, 110 Pine Ave West, Montreal, Quebec H2W 1R7, Canada
    Nat Rev Drug Discov 11:367-83. 2012
    The mammalian proprotein convertases constitute a family of nine secretory serine proteases that are related to bacterial subtilisin and yeast kexin...
  2. 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...
  3. ncbi ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs
    J Ye
    Department of Molecular Genetics, University of Texas, Southwestern Medical Center, Dallas, TX 75390, USA
    Mol Cell 6:1355-64. 2000
    ..ATF6 processing did not require SCAP, which is essential for SREBP processing. We conclude that S1P and S2P are required for the ER stress response as well as for lipid synthesis...
  4. 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
    ..PCSK9 encodes NARC-1 (neural apoptosis regulated convertase), a newly identified human subtilase that is highly expressed in the liver and contributes to cholesterol homeostasis...
  5. 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
    ..1%) and were associated with a 40% reduction in plasma levels of LDL cholesterol. These data indicate that common sequence variations have large effects on plasma cholesterol levels in selected populations...
  6. ncbi Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibiti
    Frederick Raal
    Carbohydrate and Lipid Metabolism Research Unit, Division of Endocrinology and Metabolism, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa
    Circulation 126:2408-17. 2012
    ..This phase 2, multicenter, double-blind, randomized, placebo-controlled, dose-ranging study evaluated the efficacy and safety of AMG 145 in heterozygous familial hypercholesterolemia patients...
  7. ncbi Effect of a monoclonal antibody to PCSK9 on LDL cholesterol
    Evan A Stein
    Metabolic and Atherosclerosis Research Center, 4685 Forest Ave, Cincinnati, OH 45212, USA
    N Engl J Med 366:1108-18. 2012
    ..We report three phase 1 studies of a monoclonal antibody to PCSK9 designated as REGN727/SAR236553 (REGN727)...
  8. 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
    ..As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded...
  9. pmc Increasing serum half-life and extending cholesterol lowering in vivo by engineering antibody with pH-sensitive binding to PCSK9
    Javier Chaparro-Riggers
    Rinat Pfizer Inc, South San Francisco, California 94080, USA
    J Biol Chem 287:11090-7. 2012
    ..Engineered pH-sensitive antibodies may enable less frequent or lower dosing of antibodies hampered by target-mediated clearance and high antigen load...
  10. 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...
  11. 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 2 other known genes implicated in ADH encode the low-density lipoprotein receptor and apolipoprotein B. As an approach toward the elucidation of the physiological role(s) of NARC-1, we studied its transcriptional regulation...
  12. pmc Endoproteolytic processing of the lymphocytic choriomeningitis virus glycoprotein by the subtilase SKI-1/S1P
    Winfried R Beyer
    Heinrich Pette Institut fur experimentelle Virologie und Immunologie an der Universitat Hamburg, D 20251 Hamburg, Germany
    J Virol 77:2866-72. 2003
    ..In agreement with the identified consensus motif, we show that the cellular subtilase SKI-1/S1P cleaves LCMV GP...
  13. 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
    ..We conclude that secreted PCSK9 associates with the LDLR and reduces hepatic LDLR protein levels...
  14. 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
    ..These data enhance our understanding of the functional role of the acidic prosegment and on the effect of pH in the regulation of PCSK9 activity...
  15. ncbi Novel loss-of-function PCSK9 variant is associated with low plasma LDL cholesterol in a French-Canadian family and with impaired processing and secretion in cell culture
    Janice Mayne
    Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada
    Clin Chem 57:1415-23. 2011
    ..We studied the clinical and molecular characteristics of a novel PCSK9 loss-of-function sequence variant in a white French-Canadian family...
  16. ncbi Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlle
    Evan A Stein
    Metabolic and Atherosclerosis Research Center, Cincinnati, OH 45212, USA
    Lancet 380:29-36. 2012
    ..We assessed the efficacy and safety of various doses and dosing intervals of REGN727, a monoclonal antibody to PCSK9, added to statins, to further lower LDL-C in patients with heterozygous familial hypercholesterolaemia...
  17. 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
    ..PCSK9 may diminish LDL receptors by a mechanism that requires direct binding but not necessarily receptor proteolysis...
  18. 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
    ..In conclusion, NARC-1 seems to affect both the level of LDLR and that of circulating apoB-containing lipoproteins in an LDLR-dependent and -independent fashion...
  19. pmc Proinsulin processing by the subtilisin-related proprotein convertases furin, PC2, and PC3
    S P Smeekens
    Howard Hughes Medical Institute, Department of Biochemistry, University of Chicago, IL 60637
    Proc Natl Acad Sci U S A 89:8822-6. 1992
    ..cells with recombinant vaccinia virus expressing human furin, human PC2, mouse PC3 (subtilisin-related proprotein convertases 1-3, respectively), or yeast Kex2 indicate that in this system both Kex2 and furin produce mature insulin, ..
  20. 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
    ..Finally, the PCSK9-LDLR complex appears not to be transported by the canonical ESCRT pathway...
  21. 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 mammalian secretory proprotein convertases are part of a family of nine serine proteinases of the subtilisin-type. Seven of them cleave after basic amino acids and are called PC1/3, PC2, furin, PC4, PC5/6, PACE4 and PC7...
  22. pmc Antiviral activity of a small-molecule inhibitor of arenavirus glycoprotein processing by the cellular site 1 protease
    Shuzo Urata
    Department of Immunology and Microbial Science IMM 6, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Virol 85:795-803. 2011
    ..Our findings support the feasibility of using small-molecule inhibitors of S1P-mediated processing of arenavirus GPC as a novel antiviral strategy...
  23. ncbi The proprotein convertases, 20 years later
    Nabil G Seidah
    Biochemical Neuroendocrinology Laboratory, Clinical Research Institute of Montreal, Montreal, QC, Canada H2W 1R7
    Methods Mol Biol 768:23-57. 2011
    The proprotein convertases (PCs) are secretory mammalian serine proteinases related to bacterial subtilisin-like enzymes. The family of PCs comprises nine members, PC1/3, PC2, furin, PC4, PC5/6, PACE4, PC7, SKI-1/S1P, and PCSK9 (Fig. 3.1)...
  24. 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
    ..The latter may reduce the lifetime of this proteinase and its ability to degrade the cell-surface LDL receptor, thereby regulating the levels of circulating LDL cholesterol...
  25. pmc The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P
    O Lenz
    Institute of Virology, Philipps University, Robert Koch Strasse 17, 35037 Marburg, Germany
    Proc Natl Acad Sci U S A 98:12701-5. 2001
    ..To our knowledge, there have been no previous reports of this type of viral glycoprotein processing, one that may be an interesting target for antiviral therapy...
  26. 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
    ..These findings reveal that PCSK9 activity is a major determinant of plasma levels of LDL-C in humans and make it an attractive therapeutic target for LDL-C lowering...
  27. 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
    ..PCSK9 is present in human plasma, but the factors that contribute to differences in plasma concentrations of PCSK9 and how they impact on the levels of lipoproteins have not been well-characterized...
  28. 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
    ..Thus, this study demonstrates a more general effect of PCSK9 on the degradation of the LDLR family that emphasizes its major role in cholesterol and lipid homeostasis as well as brain development...
  29. ncbi 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
    ..The underlying mechanism could involve the binding of this peptide segment to positively charged structures which are important for PCSK9's activity. One possible candidate could be the histidine-rich C-terminal domain of PCSK9...
  30. 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
    ..Thus, domains in both the LDLR and PCSK9 that are not required for binding (or internalization) are essential for PCSK9-mediated degradation of the LDLR...
  31. 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
    ..The very low plasma level of LDL-C and apparent good health of this individual demonstrate that PCSK9 plays a major role in determining plasma levels of LDL-C and provides an attractive target for LDL-lowering therapy...
  32. pmc Molecular biology of PCSK9: its role in LDL metabolism
    Jay D Horton
    Departments of Internal Medicine and Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9046, USA
    Trends Biochem Sci 32:71-7. 2007
    ..Although the mechanism of PCSK9 action is not yet clear, the protease provides a new therapeutic target to lower plasma levels of LDL and prevent CHD...
  33. ncbi Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice
    Mark J Graham
    Cardiovascular Group, Department of Antisense Drug Discovery, Isis Pharmaceuticals, Inc, Carlsbad, CA 92008, USA
    J Lipid Res 48:763-7. 2007
    ..Antisense inhibition of PCSK9 is an attractive and novel therapeutic approach for treating hypercholesterolemia in human...
  34. 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 that affect this transport can lead to hyper- or hypocholesterolemia...
  35. 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
    ..However, lipid accumulation in hepatocytes of these mice was markedly reduced under both chow and high-cholesterol diets, revealing that PCSK9 deficiency confers resistance to liver steatosis...
  36. pmc A new method for measurement of total plasma PCSK9: clinical applications
    Geneviève Dubuc
    Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Montreal, Quebec, Canada
    J Lipid Res 51:140-9. 2010
    ..316, P < 0.02 in FH and r = 0.275, P < 0.009 in non-FH). The detection of circulating PCSK9 in both FH and non-FH subjects means that this assay could be used to monitor response to therapy in a wide range of patients...
  37. ncbi 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
    ..Finally, we present future prospects concerning this therapeutic target that might constitute a new approach to reduce cholesterol levels and CHD, and enhance the effectiveness of other lipid-lowering drugs...
  38. pmc 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
    ..In cynomolgus monkeys, a single injection of mAb1 reduces serum LDL-C by 80%, and a significant decrease is maintained for 10 days. We conclude that anti-PCSK9 antibodies may be effective therapeutics for treating hypercholesterolemia...
  39. pmc Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9
    Shirya Rashid
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9046, USA
    Proc Natl Acad Sci U S A 102:5374-9. 2005
    ..These data demonstrate that PCSK9 regulates the amount of LDLR protein in liver and suggest that inhibitors of PCSK9 may act synergistically with statins to enhance LDLRs and reduce plasma cholesterol...
  40. 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
    ..Thus, PCSK9 seems to hold LDLR in an extended conformation and to interfere with conformational rearrangements required for LDLR recycling...
  41. 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
    ..However, in vivo, it is suggested that the sterol-dependent regulation of PCSK9 is mediated predominantly by SREBP-2...
  42. pmc High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol
    Greg Welder
    University of Florida, Gainesville, FL, USA
    J Lipid Res 51:2714-21. 2010
    ..Together, these results further suggest an explanation for why increasing doses of statins fail to achieve proportional LDL-C lowering...
  43. 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
    ..The C-terminal domain of PCSK9 has a novel protein fold and may mediate protein-protein interactions. The structure of PCSK9 provides insight into its biochemical characteristics and biological function...
  44. ncbi Mechanisms for lymphocytic choriomeningitis virus glycoprotein cleavage, transport, and incorporation into virions
    Stefan Kunz
    The Scripps Research Institute, Division of Virology, Department of Neuropharmacology, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Virology 314:168-78. 2003
    ..The effect of the truncation of the cytoplasmic tail on cleavage suggests a structural interdependence between the cytoplasmic domain and the ectodomains of LCMVGP...
  45. ncbi Proprotein convertases: lessons from knockouts
    Nathalie Scamuffa
    INSERM U716 Equipe AVENIR, Institut de Genetique Moleculaire, 27 rue Juliette Dodu, 75010 Paris, France
    FASEB J 20:1954-63. 2006
    The physiological role of the subtilisin/kexin-like proprotein convertases (PCs) in rodents has been examined through the use of knockout mice...
  46. ncbi Differential processing of pro-neurotensin/neuromedin N and relationship to pro-hormone convertases
    Patrick Kitabgi
    INSERM U732, Universite Pierre et Marie Curie, Hopital St Antoine, 184 rue du Faubourg St Antoine, 75571 Paris Cedex 12, France
    Peptides 27:2508-14. 2006
    ..As NT, NN, large NT and large NN are all endowed with biological activity, the evidence reviewed here supports the idea that post-translational processing of pro-NT/NN in tissues may generate biological diversity...
  47. pmc Plasma PCSK9 levels are significantly modified by statins and fibrates in humans
    Janice Mayne
    Chronic Disease Program, Ottawa Health Research Institute, The Ottawa Hospital, University of Ottawa, Ottawa, Ontario, Canada
    Lipids Health Dis 7:22. 2008
    ..PCSK9 circulates in human plasma, and we previously reported that plasma PCSK9 is positively correlated with total cholesterol and LDLC in men...
  48. pmc Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype
    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 101:7100-5. 2004
    ....
  49. 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
    ..These results suggest that the addition of a PCSK9 inhibitor to statin therapy may result in even further LDL-C decreases...
  50. ncbi Gene inactivation of proprotein convertase subtilisin/kexin type 9 reduces atherosclerosis in mice
    Maxime Denis
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave W, Montreal, QC, H2W 1R7, Canada
    Circulation 125:894-901. 2012
    ..This suggests that lowering PCSK9 may protect against atherosclerosis...
  51. 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...
  52. pmc Proprotein convertase subtilisin/kexin type 9 (PCSK9) can mediate degradation of the low density lipoprotein receptor-related protein 1 (LRP-1)
    Maryssa Canuel
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, affiliated to the University of Montreal, Montreal, Quebec, Canada
    PLoS ONE 8:e64145. 2013
    ..Identification of PCSK9 targets should allow a better understanding of the consequences of PCSK9 inhibition for lowering LDLc and tumor metastasis...
  53. 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
    ..The results showed no activity of any secreted deletant compared with PCSK9. Thus, although M2 is dispensable for secretion, its presence is required for the extracellular activity of PCSK9 on cell surface LDLR...
  54. ncbi Proprotein convertase subtilisin/kexin type 9 interacts with apolipoprotein B and prevents its intracellular degradation, irrespective of the low-density lipoprotein receptor
    Hua Sun
    University of Texas Graduate School of Biomedical Sciences at Houston, USA
    Arterioscler Thromb Vasc Biol 32:1585-95. 2012
    ..To date, the relationship between PCSK9 and metabolism of apolipoprotein B (apoB), the structural protein of LDL, has been controversial and remains to be clarified...
  55. 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
    ..Finally, we identified an AnxA2 coding polymorphism, V98L, that correlates with lower circulating levels of PCSK9 thereby extending our results on the physiological role of AnxA2 in humans...
  56. ncbi PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling
    Kai Kysenius
    Neuroscience Center, University of Helsinki, Viikinkaari 4, P O Box 56, 00014, Helsinki, Finland
    Cell Mol Life Sci 69:1903-16. 2012
    ..We conclude that PCSK9 potentiates neuronal apoptosis via modulation of ApoER2 levels and related anti-apoptotic signaling pathways...
  57. ncbi Circulating proprotein convertase subtilisin/kexin 9 (PCSK9) regulates VLDLR protein and triglyceride accumulation in visceral adipose tissue
    Anna Roubtsova
    Laboratory of Biochemical Neuroendocrinology, University of Montreal, Montreal, Quebec, Canada
    Arterioscler Thromb Vasc Biol 31:785-91. 2011
    ..Herein, we investigated the role of PCSK9 in adipose tissue metabolism...
  58. 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
    ....
  59. ncbi Proprotein convertase substilisin/kexin type 9 antagonism reduces low-density lipoprotein cholesterol in statin-treated hypercholesterolemic nonhuman primates
    Hong Liang
    Rinat Laboratories, Pfizer Inc, 230 East Grand Avenue, South San Francisco, CA 94080, USA
    J Pharmacol Exp Ther 340:228-36. 2012
    ..Our data demonstrate that anti-PCSK9 antibody is a promising LDL-C-lowering agent that is both efficacious and potentially additive to current therapies...
  60. ncbi Potential of proprotein convertase subtilisin/kexin type 9 based therapeutics
    Evan A Stein
    Metabolic and Atherosclerosis Research Center and Medpace Reference Laboratories, 5355 Medpace Way, Cincinnati, OH, USA
    Curr Atheroscler Rep 15:310. 2013
    ..Larger and much longer phase 3 trials are now in progress to assess the long-term tolerability, safety, and impact on cardiovascular disease events of these very effective LDLc lowering compounds...
  61. pmc Alterations in gene expression of proprotein convertases in human lung cancer have a limited number of scenarios
    Ilya V Demidyuk
    Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia
    PLoS ONE 8:e55752. 2013
    b>Proprotein convertases (PCs) is a protein family which includes nine highly specific subtilisin-like serine endopeptidases in mammals...
  62. ncbi Clinical aspects of PCSK9
    Bertrand Cariou
    INSERM, UMR915, l institut du thorax, F 44000 Nantes, France
    Atherosclerosis 216:258-65. 2011
    ..Finally, we present a brief overview of the available therapeutic strategies to inhibit PCSK9...
  63. 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
    ..Our findings show that PCSK9 deficiency reduces liver metastasis by its ability to lower cholesterol levels and by possibly enhancing TNFα-mediated apoptosis...
  64. ncbi Arenavirus envelope glycoproteins mimic autoprocessing sites of the cellular proprotein convertase subtilisin kexin isozyme-1/site-1 protease
    Antonella Pasquato
    Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland
    Virology 417:18-26. 2011
    ..The data suggest that arenavirus GPCs evolved to mimic SKI-1/S1P autoprocessing sites, likely ensuring efficient cleavage and perhaps avoiding competition with SKI-1/S1P's cellular substrates...
  65. 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
    ..Our data also suggest that LDLR protein regulation by PCSK9 has tissue specificity, with liver being the most responsive tissue...
  66. 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
    ..All Asp(374) mutations resulted in similar gain-of-function activity on the LDLR except that D374E was as active as native PCSK9, D374G was relatively less active, and D374N and D374P were completely inactive...
  67. 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
    ..Its gene is associated with the development of familial hypercholesterolemia. mRNA silencing or inhibition of PCSK9-induced degradation of LDLR may be used to treat this disease...
  68. pmc Hepatitis C virus E1 envelope glycoprotein interacts with apolipoproteins in facilitating entry into hepatocytes
    Budhaditya Mazumdar
    Department of Internal Medicine, St Louis University, St Louis, MO, USA
    Hepatology 54:1149-56. 2011
    ....
  69. pmc Human subtilase SKI-1/S1P is a master regulator of the HCV Lifecycle and a potential host cell target for developing indirect-acting antiviral agents
    Andrea D Olmstead
    Department of Microbiology and Immunology, Life Sciences Centre, University of British Columbia, Vancouver, British Columbia, Canada
    PLoS Pathog 8:e1002468. 2012
    ....
  70. ncbi Identification of inhibitors of prohormone convertases 1 and 2 using a peptide combinatorial library
    E Apletalina
    Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans, Louisiana 70112, USA
    J Biol Chem 273:26589-95. 1998
    ....
  71. pmc A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo
    Yan G Ni
    Department of Cardiovascular Diseases, Merck Research Laboratories, Rahway, New Jersey, USA
    J Lipid Res 52:78-86. 2011
    ..Together these results clearly demonstrate that the LDL-lowering effect of the neutralizing anti-PCSK9 1D05-IgG2 antibody is mediated by reducing the amount of PCSK9 that can bind to the LDLr...
  72. pmc Proteolytic processing of angiopoietin-like protein 4 by proprotein convertases modulates its inhibitory effects on lipoprotein lipase activity
    Xia Lei
    Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA
    J Biol Chem 286:15747-56. 2011
    ..ANGPTL4 protein is then proteolytically cleaved into several forms by proprotein convertases (PCs)...
  73. pmc Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects
    Xiaorong Zhu
    Department of Biochemistry and Molecular Biology, University of Chicago, and the Howard Hughes Medical Institute, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 99:10293-8. 2002
    The subtilisin-like proprotein convertases PC1/3 (SPC3) and PC2 (SPC2) are believed to be the major endoproteolytic processing enzymes of the regulated secretory pathway...
  74. pmc Molecular characterization of the processing of arenavirus envelope glycoprotein precursors by subtilisin kexin isozyme-1/site-1 protease
    Dominique J Burri
    Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland
    J Virol 86:4935-46. 2012
    ..In sum, our study reveals important differences in the SKI-1/S1P processing of viral and cellular substrates...
  75. 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
    ..This three-dimensional homology provides insight into the function of PCSK9 at the molecular level and will help to dissect the link between PCSK9 and CHD...
  76. ncbi Increased expression of the pro-protein convertase furin predicts decreased survival in ovarian cancer
    Robert E Page
    Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Cell Oncol 29:289-99. 2007
    b>Proprotein convertases (PCs) are serine proteases that after restricted proteolysis activate many proteins that play a crucial role in cancer such as metalloproteinases, growth factors and growth factor receptors, adhesion molecules, and ..
  77. ncbi Biosynthesis and cellular trafficking of the convertase SKI-1/S1P: ectodomain shedding requires SKI-1 activity
    Aram Elagoz
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 277:11265-75. 2002
    ..In conclusion, multiple domains ensuring optimal functional characteristics control SKI-1 activity and cellular trafficking...
  78. pmc The role of single N-glycans in proteolytic processing and cell surface transport of the Lassa virus glycoprotein GP-C
    Robert Eichler
    Institut für Virologie der Philipps Universität Marburg, Hans Meerwein Str, 3, 35037 Marburg, Germany
    Virol J 3:41. 2006
    ..The findings indicate that N-glycans are needed for correct conformation of GP-C in order to be cleaved by SKI-1/S1P...
  79. ncbi 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 identification of the minimal inhibitory sequence of AnxA2 should pave the way toward the development of PCSK9 inhibitory lead molecules for the treatment of hypercholesterolemia...
  80. ncbi What lies ahead for the proprotein convertases?
    Nabil G Seidah
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Canada
    Ann N Y Acad Sci 1220:149-61. 2011
    ..In vivo studies demonstrated that PCs play major roles in health and disease states...
  81. 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
    ..We conclude that the ability of PCSK9 to degrade LDLRs is independent of catalytic activity and suggest that PCSK9 functions as a chaperone to prevent LDLR recycling and/or to target LDLRs for lysosomal degradation...
  82. 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
    ..Therefore, targeting either pathway, or both, would be an effective method to reduce PCSK9 activity in the treatment of hypercholesterolemia and coronary heart disease...
  83. ncbi Prediction of proprotein convertase cleavage sites
    Peter Duckert
    Center for Biological Sequence Analysis, BioCentrum DTU, Technical University of Denmark, Building 208, DK 2800 Lyngby, Denmark
    Protein Eng Des Sel 17:107-12. 2004
    ..The method predicts cleavage sites in independent sequences with a sensitivity of 95% for the furin neural network and 62% for the general PC network. The ProP method is made publicly available at http://www.cbs.dtu.dk/services/ProP...
  84. ncbi 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
    ..PCSK9 plays a key role in plasma cholesterol metabolism by modulating the expression of LDL receptors...
  85. 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
    ..1G08 Fab represents a useful new tool for delineating the mechanism of PCSK9 uptake and LDLR degradation...
  86. pmc The proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations
    Lynn Htet Htet Aung
    Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, Guangxi, People s Republic of China
    Lipids Health Dis 10:5. 2011
    ..The present study was undertaken to detect the association of PCSK9 E670G polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations...
  87. ncbi PCSK9 and LDL cholesterol: unravelling the target to design the bullet
    Philippe Costet
    INSERM, UMR915, l institut du thorax, 1 rue Gaston Veil, Nantes, France
    Trends Biochem Sci 33:426-34. 2008
    ..Moreover, new clinical and epidemiological data have revealed the correlation between plasma PCSK9 concentrations and LDLC levels...
  88. 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...
  89. 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
    ....
  90. ncbi Molecular basis of PCSK9 function
    Gilles Lambert
    The Heart Research Institute, Camperdown, NSW 2050, Australia
    Atherosclerosis 203:1-7. 2009
    ..The present review summarizes studies published or in print before May 2008 investigating the functional significance of PCSK9 and its promising aspects as a prognostic tool and a drug target...
  91. ncbi 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
    ..Our data support the concept that the rare allele of the R46L SNP at the PCSK9 locus significantly lowers LDL C, but does not greatly reduce CHD risk in an elderly population with a high prevalence of cardiovascular disease...
  92. ncbi Fasting induces hyperlipidemia in mice overexpressing proprotein convertase subtilisin kexin type 9: lack of modulation of very-low-density lipoprotein hepatic output by the low-density lipoprotein receptor
    Gilles Lambert
    Universite de Nantes, UFR de Medecine, Institut National de la Sante et de la Recherche Medicale, Unité 539, Centre Hospitalier Universitaire Hotel Dieu, 44093 Nantes, France
    Endocrinology 147:4985-95. 2006
    ..In summary, the negative modulation of LDLr expression by PCSK9, which decreases plasma LDL clearance, also promotes an overproduction of nascent VLDL in vivo upon fasting...
  93. ncbi Inhibition of proprotein convertases: approaches to block squamous carcinoma development and progression
    Ricardo López de Cicco
    Department of Pathology and Tumor Cell Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Mol Carcinog 46:654-9. 2007
    ..PDX and CMK have also been assayed in vivo using skin carcinogenesis models. Newer promising small molecules and RNA interference approaches are also being developed to inhibit PCs...
  94. ncbi Regulation of Pcsk6 expression during the preantral to antral follicle transition in mice: opposing roles of FSH and oocytes
    Francisco J Diaz
    The Jackson Laboratory, Bar Harbor, ME 04609, USA
    Biol Reprod 78:176-83. 2008
    ..The proprotein convertases are a family of seven known proteins that process TGFbeta ligands and other secreted products to their ..
  95. ncbi Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response
    Kezhong Zhang
    Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
    Cell 124:587-99. 2006
    ..Together, our studies delineate a molecular mechanism for activation of an ER-localized transcription factor, CREBH, and reveal an unprecedented link by which ER stress initiates an acute inflammatory response...
  96. ncbi Regulation of the stepwise proteolytic cleavage and secretion of PDGF-B by the proprotein convertases
    Geraldine Siegfried
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal, Quebec, Canada H2W 1R7
    Oncogene 24:6925-35. 2005
    ..Our findings emphasize the importance of the convertase-directed processing of proPDGF-B at the RGRR81/ sequence for PDGF-B maturation and secretion...
  97. pmc Cell-surface processing of extracellular human immunodeficiency virus type 1 Vpr by proprotein convertases
    Yong Xiao
    Laboratory of Human Retrovirology, Institut de Recherches Cliniques de Montreal, Montreal, Quebec, Canada
    Virology 372:384-97. 2008
    ..Collectively, these results suggest that cell surface processing of extracellular Vpr by PCs might regulate the levels of active soluble Vpr...
  98. ncbi Shedding of collagen XXIII is mediated by furin and depends on the plasma membrane microenvironment
    Guido Veit
    Center for Biochemistry, Medical Faculty, University of Cologne, Joseph Stelzmannstrasse 52, 50931 Cologne, Germany
    J Biol Chem 282:27424-35. 2007
    ..These mechanisms allow the cell to regulate the amounts of cell surface-bound and secreted collagen XXIII...
  99. pmc SPC4/PACE4 regulates a TGFbeta signaling network during axis formation
    D B Constam
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138 USA
    Genes Dev 14:1146-55. 2000
    ..These findings establish an important role for SPC4 in patterning the early mouse embryo...
  100. ncbi Tissue distribution and processing of proSAAS by proprotein convertases
    M Sayah
    Department of Biochemistry and Molecular Biology, LSU Health Science Center, New Orleans, LA 70112, USA
    J Neurochem 76:1833-41. 2001
    ..Whereas the C-terminal peptide is mostly internally cleaved in wild-type mouse brain, it is not processed as efficiently in the brain of PC2 null mice, suggesting that PC2 is partially responsible for this cleavage in vivo...
  101. pmc 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
    ..Here we 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...

Research Grants60

  1. Deorphanizing the Peptidome
    Bryan L Roth; Fiscal Year: 2012
    ..abstract_text> ..
  2. Mechanisms regulating PKGI proteolysis and modulation of pulmonary SMC phenotype
    Jesse D Roberts; Fiscal Year: 2013
    ..Studies of the PKGI proteolysis cleavage site and the effect of substrate decoys suggest that proprotein convertases are responsible for PKGI[unreadable] nuclear localization in SMC...
  3. 2010 Proprotein Processing, Trafficking, and Secretion;Gordon Research Conferenc
    Lloyd D Fricker; Fiscal Year: 2013
    ..The identification of the enzymes--including the proprotein convertases (PCs), select carboxypeptidases, and the a-amidating enzyme --that catalyze the maturation of hundreds of ..
  4. EMBRYONIC SIGNALING REGULATION BY PROPROTEIN CONVERTASES
    Jan L Christian; Fiscal Year: 2012
    ....
  5. Furin and the Etiopathogenesis of UV-Induced Skin Cancer
    Andres J Klein-Szanto; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Furin is a protein processing enzyme of the family of proprotein convertases (PCs), which has a significant role in cancer etiopathogenesis...
  6. The role of proprotein convertases in lipid metabolism
    Weijun Jin; Fiscal Year: 2009
    ..Despite of decades of research, many aspects of lipid metabolism are incompletely understood. Proprotein convertases (PCs) were suspected to be involved in lipid metabolism, but their importance has not been fully ..
  7. Determinants of organelle-specific activation of Proprotein Convertase 1
    DANIELLE MARIE WILLIAMSON; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Proprotein convertases (PCs), such as PC1 and furin, are a ubiquitous super-family of evolutionarily conserved serine proteases responsible for mediating a diverse range of processing steps to ..
  8. PTHRP 1 to 173 IN CHONDROCYTES
    Robert Terkeltaub; Fiscal Year: 2005
    ..In doing so, we will test the hypothesis that furin-like subtilisin family proprotein convertases (PCs) are at least partially responsible...
  9. OPIATE PRECURSOR PROCESSING
    Vivian Hook; Fiscal Year: 1999
    ..Overall these studies will establish the relative importance of PTP, compared to PC 1/3 and PC2, in PE processing. ..
  10. Specificity of Subtilisin-like Proprotein Convertases
    JOSEPH SUCIC; Fiscal Year: 2003
    Subtilisin-like proprotein convertases (SPCs) are endoproteases that function within the secretory pathway of eucaryotic cells...
  11. Metabolic Modulation of Vision
    Robert Barlow; Fiscal Year: 2009
    ..abstract_text> ..
  12. PRENATAL DIFFERENTIATION OF THE PITUITARY GLAND
    John Pintar; Fiscal Year: 2002
    ....
  13. Molecular Target(s) for Interruption of HBV Infection
    Jisu Li; Fiscal Year: 2009
    ..Determine the contribution of proprotein convertases to DHBV infectivity;and (3)...
  14. METABOLIC CONSEQUENCES OF A PROHORMONE PROCESSING DEFECT
    JUERGEN NAGGERT; Fiscal Year: 2002
    ....
  15. MOLECULAR GENETICS OF HUMAN ARPKD
    Feng Qian; Fiscal Year: 2009
    ..In Aim 1, we will test the hypothesis that PD undergoes regulated proteolysis mediated by proprotein convertases, TACE or other metalloprotease, and secretase using a variety of epitope-tagged recombinant molecules, ..
  16. Furin Inhibition in HIV Disease
    Seth Pincus; Fiscal Year: 2006
    ..gpl60, is cleaved into the mature forms, gp120 and gp41, by the cellular protease furin and furin-like proprotein convertases (PPCs)...
  17. 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. ..
  18. ProTRH sorting to the regulated secretory pathway
    EDUARDO NILLNI; Fiscal Year: 2006
    ..The sorting of the proTRH N- and C-terminal fragments is routed to two different pathways. Aim 4. The tertiary structure of proTRH contributes to its processing by PC1 and PC2 and further sorting to the RSP. ..
  19. POMC Processing and Beta-Endorphine-Related Opioid Peptides
    Vivian Y H Hook; Fiscal Year: 2010
    ..New findings from this project will enhance our knowledge of the complexity of biosynthetic mechanisms for endogenous opioid and neuropeptide systems. ..
  20. Serpin Protease Inhibitors & Opioid Neuropeptides
    Vivian Hook; Fiscal Year: 2006
    ..Serpin regulation of opioid peptides that mediate analgesia and stress may lead to development of new therapeutic approaches in pain and neurologic disease. ..
  21. BIOSYNTHESIS OF ENKEPHALIN OPIOID PEPTIDES
    Vivian Hook; Fiscal Year: 2009
    ..These findings will enhance our knowledge of the complexity of the endogenous opioid system. ..
  22. INTEGRATED DNA SEQUENCING SYSTEM
    Vivian Hook; Fiscal Year: 2002
    ..abstract_text> ..
  23. PROTRH GENE TRANSCRIPTION AND BIOSYNTHESES BY LEPTIN
    EDUARDO NILLNI; Fiscal Year: 2008
    ..B) Since the melanocortin system represents the indirect pathway of action on TRH neurons, we will also determine whether alpha- MSH affects the biosynthesis, maturation and activity of PCI, PC2, proSAAS, 7B2 and CPE. ..
  24. CCK in Generating Enzyme - Structure, Location and Role
    Margery Beinfeld; Fiscal Year: 2005
    ..The effect of this inhibition on the processing of pro CCK will be determined. ..
  25. Proteomics/Genomics of Opiate Analgesia and Addiction
    Vivian Hook; Fiscal Year: 2004
    ..Elucidation of distinct pathways will be significant, since it could allow future design of opiate drug regimens that provide effective analgesia, without the tolerance and dependence of addiction. ..
  26. BAG-75: UNIQUE MARKER OF PRIMARY BONE FORMATION
    JEFFREY GORSKI; Fiscal Year: 2003
    ..Stimulation of appositional formation by lamellar bone would not be expected to have the same effect. These future functional studies require determination of the BAG-75 cDNA sequence. ..
  27. MINERALIZATION OF PRIMARY BONE
    JEFFREY GORSKI; Fiscal Year: 2008
    ..Results of this work should better define the differences between primariy and lamellar bone, as well as aid in the diagnosis and treatment of osteoporosis and atherosclerosis. ..
  28. 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. ..
  29. Regulation of Tangential Migration in the Embryonic CNS
    Andrew Peterson; Fiscal Year: 2004
    ..abstract_text> ..
  30. Structure-based Drug Design for Smallpox Therapy
    Alex Strongin; Fiscal Year: 2008
    ..When appropriate benchmarks are met, the drug candidates will be delivered to the government for continued testing and refinement involving the variola virus. [unreadable] [unreadable]..
  31. GENETIC EPIDEMIOLOGY OF CHANGE IN CVD RISK FACTORS
    DAVID MICHAEL HALLMAN; Fiscal Year: 2010
    ....
  32. MT1-MMP pericellular proteolysis in malignancy
    Alex Strongin; Fiscal Year: 2009
    ..The results of these experiments have a very high probability of providing an effective means to regulate the MT1-MMP function in the setting of the disease. ..
  33. Structure and Function in Notch Signaling
    STEPHEN BLACKLOW; Fiscal Year: 2008
    ..Aim 3. Investigate the functional implications of Notch dimerization in models of differentiation and disease pathogenesis. ..
  34. Targeting the PEX Domain of MT1-MMP: Novel Cancer Therapy
    Jian Cao; Fiscal Year: 2010
    ..I propose that the current project will help us to better understand cancer progression and lead to the development of novel basic tools for treatment of early stage cancer. ..
  35. CELL BIOLOGY OF CARBOXYPEPTIDASE D
    Lloyd Fricker; Fiscal Year: 2003
    ..This will provide a better understanding of the proteins, either known or novel, that interact with CPD. These studies on CPD will advance our knowledge of protein trafficking in neuroendocrine cells. ..
  36. 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. ..
  37. Genotypes, Haplotypes, and Blood Pressure Change from Childhood to Adulthood
    DAVID MICHAEL HALLMAN; Fiscal Year: 2010
    ....
  38. Function of Carboxypeptidase D
    Lloyd Fricker; Fiscal Year: 2008
    ..The overall goal of this proposal is to understand the role of each domain within CPD, using a simple organism for which CPD mutants exist and which is amenable to transgenic analysis. ..
  39. Peptidomics of Cocaine and Amphetamine Abuse
    Lloyd Fricker; Fiscal Year: 2005
    ..Taken together, these studies will provide a better understanding of the regulation of neuropeptides, both known and novel, in drug abuse. ..
  40. Estrogen, HDL, and coronary heart disease in women
    Stefania Lamon Fava; Fiscal Year: 2005
    ..The proposed analyses provide a unique opportunity to shed light on the physiological role of HDL subpopulations and HRT on CHD in women. ..
  41. THE CRES GENE IN REPRODUCTION
    Gail Cornwall; Fiscal Year: 2005
    ..abstract_text> ..
  42. Quantitative Peptidomics of Food Deprivation
    Lloyd Fricker; Fiscal Year: 2005
    ..The studies in this initial R21 will provide an unbiased survey of neuropeptides that are altered by food deprivation, and which may therefore be involved in regulating food intake and/or body weight. ..
  43. OXIDATION RISK FACTORS AND IMT PROGESSION IN FH
    Paul Hopkins; Fiscal Year: 2004
    ..Our major hypothesis is that IMT progression will be strongly related to the balance of pro-oxidant and antioxidant factors. The newly added imaging techniques will allow us to compare and contrast results using these endpoints as well. ..
  44. Hypothalamic Regulation of Energy Homeostasis
    Sharon Wardlaw; Fiscal Year: 2004
    ..Our proposed studies of P0MG regulation and processing in the rodent should thus have implications for the regulation of food intake and body weight in the human. ..
  45. Blockade of Anthrax Cytotoxicity Using Furin Inhibitors
    Iris Lindberg; Fiscal Year: 2003
    ..abstract_text> ..
  46. 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. ..
  47. OPIOID PEPTIDE PROCESSING ENZYMES
    Iris Lindberg; Fiscal Year: 2002
    ..Taken together, these experiments should help us to understand the basic biochemistry of the prohormone convertases on opioid peptide precursors as well as the regulation of convertase activity. ..
  48. Develop Effective Inhibitors of Anthrax Lethal Factor
    Alex Strongin; Fiscal Year: 2006
    ..We are confident that the resulting LF antagonist(s) will efficiently and safely provide the therapy that is so urgently required. ..
  49. Specificity of propeptide converting enzymes.
    ROBERT MACKIN; Fiscal Year: 2006
    ..abstract_text> ..
  50. Hydroxamate-based therapy to target T cell homing in IDDM
    Alex Strongin; Fiscal Year: 2007
    ..We strongly believe that the results of [unreadable] our experimental program will lead to the development of new and effective anti-diabetic therapies for IDDM patients. [unreadable] [unreadable] [unreadable]..
  51. THE CRES GENE IN REPRODUCTION
    Gail Cornwall; Fiscal Year: 2007
    ..Also, the newly purchased mass spec will enable on site protein analysis for the studies described above. In short, the environment at TTUHSC is exceptional and will fully support my proposed studies. ..
  52. Risk Burden of Lipoprotein Metabolic Gene Haplotypes
    Jeffrey Anderson; Fiscal Year: 2007
    ..We believe this thorough, novel approach will lead to a major advance in genetic CHD risk assessment, enabling the vision of gene-based medicine for CHD to be realized. [unreadable] [unreadable]..
  53. Characterization of Microsomal Fatty Acid Elongation
    JAY HORTON; Fiscal Year: 2007
    ..abstract_text> ..
  54. Pathogenesis of Obesity and Metabolic Syndrome
    JAY HORTON; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  55. CYTOKINES AND HYPOTHALAMIC-PITUITARY-IMMUNE INTERACTIONS
    Sharon Wardlaw; Fiscal Year: 2007
    ..An understanding of the endogenous hormonal mechanisms which regulate this inflammatory cytokine cascade is thus relevant to a broad range of human diseases [unreadable] [unreadable]..
  56. Taskforce for Obesity Research at Southwestern (RMI)
    JAY HORTON; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  57. Structure and Function of the LDL Receptor
    STEPHEN BLACKLOW; Fiscal Year: 2006
    ..Determine how the ligand-binding modules of the LDL receptor recognize apolipoprotein E (apoE)-containing ligands. 2. Elucidate the mechanism of ligand release by the LDLR at low pH. ..
  58. Oncogenic Notch Signaling: Structural Studies
    STEPHEN BLACKLOW; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  59. REGULATION OF NEUROPEPTIDE PROCESSING ENZYMES
    Lloyd Fricker; Fiscal Year: 2002
    ..The results of these studies will provide a better understanding of the enzymes involved with peptide biosynthesis. ..