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

Research Grants

  1. THE CRES GENE IN REPRODUCTION
    Gail Cornwall; Fiscal Year: 2005
  2. PTHRP 1 to 173 IN CHONDROCYTES
    Robert Terkeltaub; Fiscal Year: 2005
  3. THE CRES GENE IN REPRODUCTION
    Gail Cornwall; Fiscal Year: 2007
  4. ENZYMES INVOLVED IN DYNORPHIN BIOSYNTHESIS
    Lakshmi Devi; Fiscal Year: 2002
  5. A Multidisciplinary Analysis of Gelsolin Amyloid Disease
    Jeffery Kelly; Fiscal Year: 2006
  6. REGULATION OF PROTEIN TRAFFIC IN NEUROENDOCRINE CELLS
    Gary Thomas; Fiscal Year: 2001
  7. Mechanisms regulating PKGI proteolysis and modulation of pulmonary SMC phenotype
    Jesse D Roberts; Fiscal Year: 2010
  8. Specificity of Subtilisin-like Proprotein Convertases
    JOSEPH SUCIC; Fiscal Year: 2003
  9. Metabolic Modulation of Vision
    Robert Barlow; Fiscal Year: 2009
  10. Metabolic Modulation of Vision
    Robert Barlow; Fiscal Year: 2007

Detail Information

Publications239 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
    ..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...
  3. 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...
  4. doi 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)...
  5. 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...
  6. doi 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)...
  7. 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...
  8. 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...
  9. doi 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...
  10. 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...
  11. 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...
  12. 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...
  13. 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...
  14. doi The activation and physiological functions of the proprotein convertases
    Nabil G Seidah
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada
    Int J Biochem Cell Biol 40:1111-25. 2008
    The 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...
  15. doi 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...
  16. 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...
  17. 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...
  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. 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...
  20. 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...
  21. 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...
  22. doi 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...
  23. doi 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...
  24. 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...
  25. 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...
  26. 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...
  27. 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, ..
  28. 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...
  29. 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...
  30. 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...
  31. doi 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...
  32. 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...
  33. 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...
  34. 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...
  35. 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
    ....
  36. 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...
  37. 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...
  38. 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...
  39. doi 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...
  40. 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...
  41. 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...
  42. 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...
  43. 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
    ....
  44. 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...
  45. 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
    ....
  46. 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
    ....
  47. 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...
  48. 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...
  49. 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)...
  50. 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...
  51. 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...
  52. doi Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels
    Gaetan Mayer
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 283:31791-801. 2008
    ..The 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...
  53. 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 ..
  54. 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...
  55. 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...
  56. 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...
  57. 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...
  58. doi Effects of PCSK9 variants on common carotid artery intima media thickness and relation to ApoE alleles
    Giuseppe Danilo Norata
    Department of Pharmacological Sciences, Universita degli Studi di Milano, Via Balzaretti 9, Milan, Italy
    Atherosclerosis 208:177-82. 2010
    ..PCSK9 plays a key role in plasma cholesterol metabolism by modulating the expression of LDL receptors...
  59. doi 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...
  60. doi 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...
  61. 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...
  62. 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...
  63. 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
    ....
  64. 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 ..
  65. 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...
  66. doi 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...
  67. 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...
  68. ncbi 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...
  69. 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...
  70. 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...
  71. 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...
  72. pmc Comparative study of the binding pockets of mammalian proprotein convertases and its implications for the design of specific small molecule inhibitors
    Sun Tian
    Institute of Biomechanics School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China
    Int J Biol Sci 6:89-95. 2010
    b>Proprotein convertases are enzymes that proteolytically cleave protein precursors in the secretory pathway to yield functional proteins...
  73. ncbi Proprotein convertases are important mediators of the adipocyte differentiation of mouse 3T3-L1 cells
    Gilles Croissandeau
    Diseases of Aging Program, Ottawa Health Research Institute at Ottawa Hospital, University of Ottawa, 725 Parkdale Avenue, Ottawa, Ontario K1Y 4K9, Canada
    J Cell Sci 115:1203-11. 2002
    ..In this study, we show that expression of the proprotein convertases PACE4, PC7 and furin increases when 3T3-L1 cells are induced to differentiate into adipocytes...
  74. 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...
  75. 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...
  76. pmc Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein convertase with a unique cleavage specificity and cellular localization
    N G Seidah
    Laboratory of Biochemical, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, QC, Canada H2W 1R7
    Proc Natl Acad Sci U S A 96:1321-6. 1999
    ..In vitro studies suggest that SKI-1 is a Ca2+-dependent serine proteinase exhibiting a wide pH optimum for cleavage of pro-brain-derived neurotrophic factor...
  77. ncbi Histidine-rich human salivary peptides are inhibitors of proprotein convertases furin and PC7 but act as substrates for PC1
    A Basak
    Laboratory of Structure and Metabolism of Neuropeptides, Clinical Research Institute of Montreal, Quebec, Canada
    J Pept Res 49:596-603. 1997
    ..The behavior of these five peptides was examined with three proprotein convertases (PC's) which possess cleavage specificity directed towards single and pairs of basic residues...
  78. pmc Bioactivation of Müllerian inhibiting substance during gonadal development by a kex2/subtilisin-like endoprotease
    M W Nachtigal
    Department of Physiology, Program in Developmental Biology, University of California, San Francisco 94143 0444, USA
    Proc Natl Acad Sci U S A 93:7711-6. 1996
    ..Our results suggest that MIS is a natural substrate for PC5, thereby supporting a role for prohormone convertases in the activation of transforming growth factor beta-related hormones during development...
  79. ncbi Localization of prohormone convertases 1/3 and 2 in the human pituitary gland and pituitary adenomas: analysis by immunohistochemistry, immunoelectron microscopy, and laser scanning microscopy
    I Takumi
    Department of Neurosurgery, Nippon Medical School, Sendagi, Tokyo, Japan
    Mod Pathol 11:232-8. 1998
    ..The high incidence of PC1/3 and PC2 in nonfunctioning adenomas might be related to the processing of chromogranin A...
  80. ncbi Identification and functional expression of a new member of the mammalian Kex2-like processing endoprotease family: its striking structural similarity to PACE4
    T Nakagawa
    Institute of Applied Biochemistry, University of Tsukuba, Ibaraki
    J Biochem 113:132-5. 1993
    ..Transfection experiments revealed that PC6 was capable of cleaving precursors at dibasic sites. These observations suggest that PC6 is a candidate for a processing endoprotease responsible for the maturation of gastrointestinal peptides...
  81. ncbi Effect of amino acid substitution at the P(3) and P(4) subsites of fusion proteins on kex2 protease activity
    Y Suzuki
    Suntory Institute for Medicinal Research and Development, 2716 1 Akaiwa, Chiyoda Machi, Ohra Gun, Gunma 370 0503, Japan
    Biotechnol Appl Biochem 32:53-60. 2000
    ..5 once purified in urea-free solution. Thus Kex2 exhibited extended substrate specificity beyond P(2)-P(1) in the cleavage of the fusion proteins, although it depended on the reaction conditions...
  82. ncbi The nodal precursor acting via activin receptors induces mesoderm by maintaining a source of its convertases and BMP4
    Nadav Ben-Haim
    Ecole Polytechnique Fédérale de Lausanne EPFL ISREC, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Dev Cell 11:313-23. 2006
    During early mouse development, the subtilisin-like proprotein convertases (SPC) Furin and PACE4 pattern the primitive ectoderm and visceral endoderm, presumably by activating the TGFss-related Nodal precursor...
  83. pmc Golgi and vacuolar membrane proteins reach the vacuole in vps1 mutant yeast cells via the plasma membrane
    S F Nothwehr
    Institute of Molecular Biology, University of Oregon, Eugene 97403
    J Cell Biol 129:35-46. 1995
    ..We propose a model in which Vps1p is required for formation of vesicles from the late Golgi apparatus that carry vacuolar and Golgi membrane proteins bound for the prevacuolar compartment...
  84. pmc Site-1 protease is required for cartilage development in zebrafish
    Kornelia Schlombs
    Exelixis Deutschland, Spemannstrasse 35, 72076 Tuebingen, Germany
    Proc Natl Acad Sci U S A 100:14024-9. 2003
    ..This indicates that the cartilage phenoptypes of goz are caused independently of the lipid defects...
  85. ncbi Precursor processing by kex2/furin proteases
    Nathan C Rockwell
    Department of Biological Chemistry, University of Michigan Medical Center, Room 5413 Med Sci I, 1301 East Catherine, Ann Arbor Michigan 48109, USA
    Chem Rev 102:4525-48. 2002
  86. ncbi Potential opportunity in the development of new therapeutic agents based on endogenous and exogenous inhibitors of the proprotein convertases
    Yannick Bontemps
    INSERM, U 716, Equipe Avenir, Institut de Genetique Moleculaire, Paris 75010, France
    Med Res Rev 27:631-48. 2007
    The proprotein convertases (PCs) are responsible for the endoproteolytic processing of various protein precursors (e.g...
  87. ncbi Proprotein convertases as therapeutic targets
    Michel Chretien
    University of Ottawa, The Ottawa Hospital, Ottawa Health Research Institute, Chronic Disease Program, 725 Parkdale Avenue, Ottawa, Ontario, K1Y 4E9, Canada
    Expert Opin Ther Targets 12:1289-300. 2008
    ..is principally mediated by a family of calcium-dependent serine proteases, generically known as proprotein convertases. Altered expression of these enzymes in experimental animal models and in humans has been associated with ..
  88. pmc Yeast prohormone processing enzyme (KEX2 gene product) is a Ca2+-dependent serine protease
    R S Fuller
    Department of Biochemistry, University of California, Berkeley 94720
    Proc Natl Acad Sci U S A 86:1434-8. 1989
    ..Mutant enzyme molecules lacking as many as 200 C-terminal residues still retained Ca2+-dependent protease activity and were labeled by 125I-labeled Tyr-Ala-Lys-Arg-chloromethyl ketone...
  89. ncbi Structural basis for differences in substrate selectivity in Kex2 and furin protein convertases
    Todd Holyoak
    Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA
    Biochemistry 43:2412-21. 2004
    ..In addition, several monovalent cation binding sites are identified, and a mechanism of activation of Kex2 by potassium ion is proposed...
  90. ncbi Development of protein-based inhibitors of the proprotein of convertase SKI-1/S1P: processing of SREBP-2, ATF6, and a viral glycoprotein
    Philomena Pullikotil
    Laboratories of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 279:17338-47. 2004
    ..Finally, these inhibitors were also shown to affect the processing and stability of the Crimean-Congo hemorrhagic fever virus glycoprotein...
  91. 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
    The proprotein convertases represent a family of nine proteinases, comprising seven basic amino acid-specific subtilisin-like serine proteinases related to yeast kexin, known as PC1/3, PC2, furin, PC4, PC5/6, PACE4 and PC7, and two other ..
  92. ncbi Implication of proprotein convertases in the processing and spread of severe acute respiratory syndrome coronavirus
    Eric Bergeron
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Que, Canada H2W 1R7
    Biochem Biophys Res Commun 326:554-63. 2005
    ..The membrane-bound proprotein convertases (PCs) furin, PC7 or PC5B enhanced the production of the approximately 80 kDa protein...
  93. ncbi Lipopolysaccharide mediated regulation of neuroendocrine associated proprotein convertases and neuropeptide precursor processing in the rat spleen
    Guillaume Lansac
    Departement de Pharmacologie, Faculte de Medecine, Universite de Sherbrooke, Sherbrooke, Quebec, Canada, J1H 5N4
    J Neuroimmunol 171:57-71. 2006
    Within the secretory pathway, the family of proprotein convertases cleave inactive precursors at paired basic residues to generate a myriad of biologically active peptides...
  94. pmc Regulation of bone morphogenetic protein activity by pro domains and proprotein convertases
    D B Constam
    Harvard University, Department of Molecular and Cellular Biology, Cambridge, Massachusetts 02138, USA
    J Cell Biol 144:139-49. 1999
    ..Collectively, these data show that the half-life of mature BMPs is greatly influenced by the identity of their pro regions...
  95. pmc The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases
    Nadia Nour
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    Mol Biol Cell 16:5215-26. 2005
    The proprotein convertases PC5, PACE4 and furin contain a C-terminal cysteine-rich domain (CRD) of unknown function...
  96. ncbi Endo/exo-proteolysis in neoplastic progression and metastasis
    Abdel Majid Khatib
    J Mol Med (Berl) 83:856-64. 2005
    ..In recent years, growing evidence has accumulated for the important role of proprotein convertases (PCs) and peptide alpha-amidation enzymes in these processes...
  97. ncbi Proprotein convertases [corrected] are responsible for proteolysis and inactivation of endothelial lipase
    Weijun Jin
    Department of Medicine and Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, Pennyslvania 19104, USA
    J Biol Chem 280:36551-9. 2005
    ..This action is unusual for PCs, which are traditionally known as activators of pro-proteins, and highlights a potential role of PCs in lipid metabolism through their proteolytic processing of lipases...
  98. ncbi Molecular identification of the sterol-regulated luminal protease that cleaves SREBPs and controls lipid composition of animal cells
    J Sakai
    Department of Molecular Genetics, University of Texas, Southwestern Medical Center, Dallas 75235, USA
    Mol Cell 2:505-14. 1998
    ..The cDNA encodes S1P, an intraluminal 1052-amino-acid membrane-bound subtilisin-like protease. We propose that S1P is the sterol-regulated protease that controls lipid metabolism in animal cells...
  99. ncbi Cutting back on pro-protein convertases: the latest approaches to pharmacological inhibition
    Martin Fugere
    Institut de Pharmacologie de Sherbrooke, Departement de Pharmacologie, Faculte de Medecine, Universite de Sherbrooke, Sherbrooke, Quebec J1H 5N4, Canada
    Trends Pharmacol Sci 26:294-301. 2005
    ..Based on this information, we review the latest strategies to inhibit PCs, which might lead to the development of specific compounds...
  100. pmc Reduced proteolysis of secreted gelatin and Yps1-mediated alpha-factor leader processing in a Pichia pastoris kex2 disruptant
    Marc W T Werten
    Agrotechnology and Food Innovations B V, Wageningen UR, Bornsesteeg 59, NL 6708 PD Wageningen, The Netherlands
    Appl Environ Microbiol 71:2310-7. 2005
    ..pastoris kex2 and yps1 single-gene disruptants can be used for the alpha-factor leader-directed secretion of heterologous proteins otherwise degraded at basic residues...
  101. ncbi The proprotein convertase SKI-1/S1P. In vitro analysis of Lassa virus glycoprotein-derived substrates and ex vivo validation of irreversible peptide inhibitors
    Antonella Pasquato
    Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada
    J Biol Chem 281:23471-81. 2006
    ....

Research Grants75

  1. THE CRES GENE IN REPRODUCTION
    Gail Cornwall; Fiscal Year: 2005
    ..abstract_text> ..
  2. 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...
  3. 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. ..
  4. ENZYMES INVOLVED IN DYNORPHIN BIOSYNTHESIS
    Lakshmi Devi; Fiscal Year: 2002
    ....
  5. A Multidisciplinary Analysis of Gelsolin Amyloid Disease
    Jeffery Kelly; Fiscal Year: 2006
    ..Our long-term goal is to test the amyloid hypothesis in pathology by linking the cell biology and biophysical data to studies on transgenic animals and small molecule inhibitors that prevent misfolding and/or improper processing. ..
  6. REGULATION OF PROTEIN TRAFFIC IN NEUROENDOCRINE CELLS
    Gary Thomas; Fiscal Year: 2001
    ..cells compartmentalize biochemical reactions has been to study the biochemistry and cell biology of the proprotein convertases (PCS), which catalyze the proteolytic activation of peptide hormones and bioactive proteins in distinct ..
  7. Mechanisms regulating PKGI proteolysis and modulation of pulmonary SMC phenotype
    Jesse D Roberts; Fiscal Year: 2010
    ..Studies of the PKGI proteolysis cleavage site and the effect of substrate decoys suggest that proprotein convertases are responsible for PKGI? nuclear localization in SMC...
  8. 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...
  9. Metabolic Modulation of Vision
    Robert Barlow; Fiscal Year: 2009
    ..abstract_text> ..
  10. Metabolic Modulation of Vision
    Robert Barlow; Fiscal Year: 2007
    ..abstract_text> ..
  11. PRENATAL DIFFERENTIATION OF THE PITUITARY GLAND
    John Pintar; Fiscal Year: 2002
    ....
  12. Molecular Target(s) for Interruption of HBV Infection
    Jisu Li; Fiscal Year: 2009
    ..Determine the contribution of proprotein convertases to DHBV infectivity; and (3)...
  13. Furin and the Etiopathogenesis of UV-Induced Skin Cancer
    Andres J Klein Szanto; Fiscal Year: 2010
    Furin is a protein processing enzyme of the family of proprotein convertases (PCs), which has a significant role in cancer etiopathogenesis...
  14. EMBRYONIC SIGNALING REGULATION BY PROPROTEIN CONVERTASES
    Jan L Christian; Fiscal Year: 2010
    ....
  15. OPIOID PEPTIDE SYNTHESIZING ENZYMES
    Iris Lindberg; Fiscal Year: 2003
    ..abstract_text> ..
  16. CELL BIOLOGY OF BIOACTIVE PEPTIDE SECRETION
    Richard Mains; Fiscal Year: 2002
    ..Binding interactions of the pleckstrin homology and src homology 3 domains of Kalirin will be identified. ..
  17. ProSAAS,A Novel Peptide Substrate of Carboxypeptidase E
    Lloyd Fricker; Fiscal Year: 2005
    ....
  18. METABOLIC CONSEQUENCES OF A PROHORMONE PROCESSING DEFECT
    JUERGEN NAGGERT; Fiscal Year: 2002
    ....
  19. 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, ..
  20. MOLECULAR GENETICS OF HUMAN ARPKD
    Gregory Germino; Fiscal Year: 2007
    ..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, ..