serine endopeptidases

Summary

Summary: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis. EC 3.4.21.

Top Publications

  1. ncbi Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer
    Scott A Tomlins
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109 0602, USA
    Science 310:644-8. 2005
  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 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
  5. ncbi Emerging roles of proteases in tumour suppression
    Carlos Lopez-Otin
    Carlos López Otín is at the Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nat Rev Cancer 7:800-8. 2007
  6. ncbi Serine protease mechanism and specificity
    Lizbeth Hedstrom
    Department of Biochemistry, MS 009, Brandeis University, Waltham, Massachusetts 02454, USA
    Chem Rev 102:4501-24. 2002
  7. 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
  8. ncbi Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir
    Christoph Sarrazin
    Klinik fur Innere Medizin II, Universitat des Saarlandes, Homburg Saar, Germany
    Gastroenterology 132:1767-77. 2007
  9. ncbi Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2
    M Trommsdorff
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235 9046, USA
    Cell 97:689-701. 1999
  10. 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

Detail Information

Publications418 found, 100 shown here

  1. ncbi Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer
    Scott A Tomlins
    Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109 0602, USA
    Science 310:644-8. 2005
    ..These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer...
  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 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...
  5. ncbi Emerging roles of proteases in tumour suppression
    Carlos Lopez-Otin
    Carlos López Otín is at the Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    Nat Rev Cancer 7:800-8. 2007
    ..These effects are associated with more than 30 different enzymes that belong to three distinct protease classes. What are the clinical implications of these findings?..
  6. ncbi Serine protease mechanism and specificity
    Lizbeth Hedstrom
    Department of Biochemistry, MS 009, Brandeis University, Waltham, Massachusetts 02454, USA
    Chem Rev 102:4501-24. 2002
  7. 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...
  8. ncbi Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir
    Christoph Sarrazin
    Klinik fur Innere Medizin II, Universitat des Saarlandes, Homburg Saar, Germany
    Gastroenterology 132:1767-77. 2007
    ..4A protease inhibitor, has shown strong antiviral activity in phase 1 clinical studies. Because of high levels of HCV replication and the low fidelity of HCV polymerase, selection of resistant isolates during therapy may occur...
  9. ncbi Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2
    M Trommsdorff
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235 9046, USA
    Cell 97:689-701. 1999
    ..These findings suggest that VLDLR and ApoER2 participate in transmitting the extracellular Reelin signal to intracellular signaling processes initiated by mDab1...
  10. 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...
  11. doi The structural basis of mode of activation and functional diversity: a case study with HtrA family of serine proteases
    Nitu Singh
    Advanced Centre for Treatment, Research and Education in Cancer ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, India
    Arch Biochem Biophys 516:85-96. 2011
    ....
  12. pmc HtrA serine proteases as potential therapeutic targets in cancer
    Jeremy Chien
    Department Biochemistry, Sect Pathology, Via L Armanni, 5, 80138 Naples, Italy
    Curr Cancer Drug Targets 9:451-68. 2009
    ..Finally, we will discuss the potential role of epigenetic therapy in targeting the expression and activation of HtrA serine proteases and the mechanisms by which these proteases enhance cytotoxic effect of conventional chemotherapy...
  13. pmc Proteolytic activation of influenza viruses by serine proteases TMPRSS2 and HAT from human airway epithelium
    Eva Böttcher
    Institute of Virology, Philipps University, Hans Meerwein str 3, 35043 Marburg, Germany
    J Virol 80:9896-8. 2006
    ..These data suggest that TMPRSS2 and HAT are candidates for proteolytic activation of influenza viruses in vivo...
  14. 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...
  15. 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...
  16. pmc Subtilases: the superfamily of subtilisin-like serine proteases
    R J Siezen
    Department of Biophysical Chemistry, NIZO, Ede, The Netherlands
    Protein Sci 6:501-23. 1997
    ..Predictions have been updated for Ca(2+)-binding sites, disulfide bonds, and substrate specificity, based on both sequence alignment and three-dimensional homology modeling...
  17. pmc Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer
    G Attard
    Institute of Cancer Research, Male Urological Cancer Research Centre, Surrey, UK
    Oncogene 27:253-63. 2008
    ..We conclude that determination of ERG gene status, including duplication of the fusion of TMPRSS2 to ERG sequences in 2+Edel, allows stratification of prostate cancer into distinct survival categories...
  18. pmc Interaction of reelin with amyloid precursor protein promotes neurite outgrowth
    HYANG SOOK HOE
    Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057 1464, USA
    J Neurosci 29:7459-73. 2009
    ..Addition of an alpha3beta1 integrin antibody prevented APP and Reelin-induced neurite outgrowth. These findings demonstrate that Reelin interacts with APP, potentially having important effects on neurite development...
  19. ncbi Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease
    Karsten M Strauss
    Center of Neurology and Hertie Institute for Clinical Brain Research, Leicester, UK
    Hum Mol Genet 14:2099-111. 2005
    ..On the basis of functional genomics, our results provide a novel link between mitochondrial dysfunction and neurodegeneration in PD...
  20. ncbi Reelin, lipoprotein receptors and synaptic plasticity
    Joachim Herz
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texus 75390, USA
    Nat Rev Neurosci 7:850-9. 2006
    ..Here, we review the molecular mechanisms through which APOE, cholesterol, reelin and APOE receptors control synaptic functions that are essential for cognition, learning, memory, behaviour and neuronal survival...
  21. 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...
  22. ncbi A protein related to extracellular matrix proteins deleted in the mouse mutant reeler
    G D'ARCANGELO
    Roche Institute of Molecular Biology, Hoffman La Roche, Nutley, New Jersey 07110, USA
    Nature 374:719-23. 1995
    ..The encoded protein resembles extracellular matrix proteins involved in cell adhesion. The reeler phenotype thus seems to reflect a failure of early events associated with brain lamination which are normally controlled by reelin...
  23. 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...
  24. 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...
  25. doi HtrA proteases have a conserved activation mechanism that can be triggered by distinct molecular cues
    Tobias Krojer
    Research Institute of Molecular Pathology, Vienna, Austria
    Nat Struct Mol Biol 17:844-52. 2010
    ..Implications for protein quality control and regulation of oligomeric enzymes are discussed...
  26. pmc Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis
    L M Coussens
    Hormone Research Institute, University of California, San Francisco San Francisco, California 94143 0534, USA
    Genes Dev 13:1382-97. 1999
    ....
  27. ncbi Reelin and brain development
    Fadel Tissir
    Developmental Genetics Unit, Universite Catholique de Louvain, UCL 7382, 73 Avenue E Mounier, B1200 Brussels, Belgium
    Nat Rev Neurosci 4:496-505. 2003
  28. ncbi Stromal antigen targeting by a humanised monoclonal antibody: an early phase II trial of sibrotuzumab in patients with metastatic colorectal cancer
    R D Hofheinz
    Onkologisches Zentrum, III Medizinische Klinik, Universitatsklinikum Mannheim, Germany
    Onkologie 26:44-8. 2003
    ..Unconjugated sibrotuzumab (BIBH 1), which is a humanised version of the murine anti-FAP mAb F19, was investigated for its anti-tumour activity, safety and pharmacokinetics...
  29. pmc Purified lexA protein is a repressor of the recA and lexA genes
    J W Little
    Proc Natl Acad Sci U S A 78:4199-203. 1981
    ..Finally, we found that purified lexA protein was a substrate for the recA protease in a reaction requiring ATP or an analogue, adenosine 5'-[gamma-thio]triphosphate, and denatured DNA...
  30. 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...
  31. 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...
  32. ncbi Activation of Drosophila Toll during fungal infection by a blood serine protease
    Petros Ligoxygakis
    Institut de Biologie Moleculaire et Cellulaire, UPR 9022 du CNRS, 15 rue R Descartes, F67084 Strasbourg Cedex, France
    Science 297:114-6. 2002
    ..We show that ethylmethane sulfonate-induced mutations in the persephone gene, which encodes a previously unknown serine protease, block induction of the Toll pathway by fungi and resistance to this type of infection...
  33. ncbi Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases
    S Urban
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
    Cell 107:173-82. 2001
    ..Rhomboid-1 is conserved throughout evolution from archaea to humans, and our results show that a human Rhomboid promotes Spitz cleavage by a similar mechanism. This growth factor activation mechanism may therefore be widespread...
  34. pmc Cleavage of influenza virus hemagglutinin by airway proteases TMPRSS2 and HAT differs in subcellular localization and susceptibility to protease inhibitors
    Eva Böttcher-Friebertshäuser
    Institute of Virology, Philipps University Marburg, Hans Meerwein Strasse 2, 35043 Marburg, Germany
    J Virol 84:5605-14. 2010
    ..The further development of these inhibitors could lead to new drugs for influenza treatment...
  35. doi The bacterial LexA transcriptional repressor
    M Butala
    School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom
    Cell Mol Life Sci 66:82-93. 2009
    ..These may provide new starting points in the battle against the emergence of bacterial pathogens and the spread of drug resistance among them...
  36. doi Prolyl endopeptidase is involved in cellular signalling in human neuroblastoma SH-SY5Y cells
    M José Moreno-Baylach
    Division of Pharmacology and Toxicology, University of Helsinki, Helsinki, Finland
    Neurosignals 19:97-109. 2011
    ..We conclude that PREP is a regulatory target and a regulatory element in cell signalling. This is the first report of a direct influence of a cell signalling molecule, RA, on PREP expression...
  37. 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...
  38. doi Serine peptidases: classification, structure and function
    M J Page
    Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO 63110, USA
    Cell Mol Life Sci 65:1220-36. 2008
    ....
  39. pmc Reduced prostasin (CAP1/PRSS8) activity eliminates HAI-1 and HAI-2 deficiency-associated developmental defects by preventing matriptase activation
    Roman Szabo
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America
    PLoS Genet 8:e1002937. 2012
    ....
  40. pmc Membrane-anchored serine protease matriptase regulates epithelial barrier formation and permeability in the intestine
    Marguerite S Buzza
    Department of Physiology, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Proc Natl Acad Sci U S A 107:4200-5. 2010
    ..These results support a key role for matriptase in regulating intestinal epithelial barrier competence, and suggest an intriguing link between pericellular serine protease activity and tight junction assembly in polarized epithelia...
  41. pmc Evolutionary families of peptidases
    N D Rawlings
    Department of Biochemistry, Strangeways Research Laboratory, Worts Causeway, Cambridge, U K
    Biochem J 290:205-18. 1993
    ..We suggest that the classification by families could be used as an extension of the current classification by catalytic type...
  42. 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...
  43. pmc Regulation of the matriptase-prostasin cell surface proteolytic cascade by hepatocyte growth factor activator inhibitor-1 during epidermal differentiation
    Ya Wen Chen
    Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland 21201, USA
    J Biol Chem 285:31755-62. 2010
    ....
  44. pmc Separation of recombination and SOS response in Escherichia coli RecA suggests LexA interaction sites
    Anbu K Adikesavan
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS Genet 7:e1002244. 2011
    ..These new sites can provide new drug targets to modulate one or more RecA functions, with the potential to address the problem of evolution of antibiotic resistance at its root...
  45. ncbi Aeons of distress: an evolutionary perspective on the bacterial SOS response
    Ivan Erill
    Biomedical Applications Group, Centro Nacional de Microelectronica, Barcelona, Spain
    FEMS Microbiol Rev 31:637-56. 2007
    ....
  46. ncbi The HtrA family of proteases: implications for protein composition and cell fate
    Tim Clausen
    Max Planck Institut fur Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18a, 82152 Martinsried, Germany
    Mol Cell 10:443-55. 2002
    ..Here, we discuss the properties and roles of this ATP-independent protease chaperone system in protein metabolism and cell fate...
  47. doi Association of HFE and TMPRSS6 genetic variants with iron and erythrocyte parameters is only in part dependent on serum hepcidin concentrations
    Michela Traglia
    Division of Genetics and Cell Biology, San Raffaele Research Institute, Milano, Italy
    J Med Genet 48:629-34. 2011
    ..Hepcidin is the main regulator of iron homeostasis: inappropriate production of hepcidin results in iron overload or iron deficiency and anaemia...
  48. pmc PCSK9: a convertase that coordinates LDL catabolism
    Jay D Horton
    Department of Internal Medicine, The Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390 9046, USA
    J Lipid Res 50:S172-7. 2009
    ....
  49. 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...
  50. ncbi Reelin is a ligand for lipoprotein receptors
    G D'ARCANGELO
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Neuron 24:471-9. 1999
    ..In dissociated neurons, apoE reduces the level of Reelin-induced tyrosine phosphorylation of Dab1. These data suggest that Reelin directs neuronal migration by binding to VLDLR and ApoER2...
  51. pmc Serine protease HtrA1 associates with microtubules and inhibits cell migration
    Jeremy Chien
    Experimental Pathology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
    Mol Cell Biol 29:4177-87. 2009
    ..These results offer an original identification of HtrA1 as a microtubule-associated protein and provide initial mechanistic insights into the role of HtrA1 in the regulation of cell motility by modulating microtubule stability...
  52. pmc Molecular adaptation of the DegQ protease to exert protein quality control in the bacterial cell envelope
    Justyna Sawa
    Institute of Molecular Pathology, A 1030 Vienna, Austria
    J Biol Chem 286:30680-90. 2011
    ..Furthermore, our in vitro and in vivo data imply a pH-related function of DegQ in the bacterial cell envelope...
  53. pmc c-Met-induced epithelial carcinogenesis is initiated by the serine protease matriptase
    R Szabo
    Oral and Pharyngeal Cancer Branch, NIDCR, NIH, Bethesda, MD 20892, USA
    Oncogene 30:2003-16. 2011
    ..The study provides a specific example of how epithelial transformation can be promoted by epigenetic acquisition of the capacity to convert a widely available paracrine growth factor precursor to its signaling competent state...
  54. pmc Overexpression of HTRA1 leads to ultrastructural changes in the elastic layer of Bruch's membrane via cleavage of extracellular matrix components
    Sarah Vierkotten
    Center of Ophthalmology, University of Cologne, Cologne, Germany
    PLoS ONE 6:e22959. 2011
    ..It highlights the importance of ECM related proteins in the development of AMD and links HTRA1 to other AMD risk genes such as fibulin 5, fibulin 6, ARMS2 and TIMP3...
  55. pmc Neuroprotective role of the Reaper-related serine protease HtrA2/Omi revealed by targeted deletion in mice
    L Miguel Martins
    Signal Transduction Laboratory, Cancer Research UK London Research Institute, United Kingdom
    Mol Cell Biol 24:9848-62. 2004
    ....
  56. ncbi A giant protease with potential to substitute for some functions of the proteasome
    E Geier
    Max Planck Institute of Immunobiology, Stubeweg 51, D 79108 Freiburg, Germany
    Science 283:978-81. 1999
    ..In addition, TPPII may be able to substitute for some metabolic functions of the proteasome...
  57. pmc Nuclear receptor-induced chromosomal proximity and DNA breaks underlie specific translocations in cancer
    Chunru Lin
    Howard Hughes Medical Institute, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093 0648, USA
    Cell 139:1069-83. 2009
    ..Our data suggest that the confluence of two parallel pathways initiated by liganded nuclear receptor and genotoxic stress underlies nonrandom tumor translocations, which may function in many types of tumors and pathological processes...
  58. pmc The serine protease TMPRSS6 is required to sense iron deficiency
    Xin Du
    Department of Genetics, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 320:1088-92. 2008
    ..TMPRSS6 is an essential component of a pathway that detects iron deficiency and blocks Hamp transcription, permitting enhanced dietary iron absorption...
  59. ncbi Interactions of mast cell tryptase with thrombin receptors and PAR-2
    M Molino
    Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 272:4043-9. 1997
    ..Tryptase is the first protease other than trypsin that has been shown to activate human PAR-2. Its presence within mast cell granules places it in tissues where PAR-2 is expressed but trypsin is unlikely to reach...
  60. 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...
  61. ncbi The catalytic triad of serine peptidases
    L Polgar
    Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, P O Box 7, 1518, Budapest 112, Hungary
    Cell Mol Life Sci 62:2161-72. 2005
    ..The variations illustrate how different groups and different protein structures achieve the same reaction...
  62. pmc Initiation of apoptosis by granzyme B requires direct cleavage of bid, but not direct granzyme B-mediated caspase activation
    V R Sutton
    Cancer Immunology Laboratory, Peter MacCallum Cancer Institute, Melbourne 8006, Australia
    J Exp Med 192:1403-14. 2000
    ..Overall, our results indicate that mitochondrial perturbation by Bid is necessary to achieve a lethal threshold of caspase activity and cell death due to granzyme B...
  63. ncbi Two proteases defining a melanization cascade in the immune system of Drosophila
    Huaping Tang
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA
    J Biol Chem 281:28097-104. 2006
    ..We have also shown that the melanization reaction activated by MP1 and MP2 plays an important role in augmenting the effectiveness of other immune reactions, thereby promoting resistance of Drosophila to microbial infection...
  64. ncbi SOS mutator DNA polymerase IV functions in adaptive mutation and not adaptive amplification
    G J McKenzie
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030 3411, USA
    Mol Cell 7:571-9. 2001
    ..We show that pol IV, together with the major replicase, pol III, can account for all adaptive point mutations at lac. The results identify a role for pol IV in inducible genetic change...
  65. 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...
  66. 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...
  67. ncbi Neuronal position in the developing brain is regulated by mouse disabled-1
    B W Howell
    Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Nature 389:733-7. 1997
    ..Because mDab1 is expressed in wild-type cortical neurons, and Reelin expression is normal in mdab1 mutants, mDab1 may be part of a Reelin-regulated or parallel pathway that controls the final positioning of neurons...
  68. ncbi Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation
    T Hiesberger
    Department of Molecular Genetics, UT Southwestern Dallas, Texas 75235, USA
    Neuron 24:481-9. 1999
    ..Taken together, these findings suggest that Reelin acts via VLDLR and ApoER2 to regulate Disabled-1 tyrosine phosphorylation and microtubule function in neurons...
  69. ncbi Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine
    Tobias Krojer
    Max Planck Institut fur Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18a, 82152 Martinsried, Germany
    Nature 416:455-9. 2002
    ..In the chaperone conformation, the protease domain of DegP exists in an inactive state, in which substrate binding in addition to catalysis is abolished...
  70. pmc Common variants in TMPRSS6 are associated with iron status and erythrocyte volume
    Beben Benyamin
    Queensland Institute of Medical Research, Brisbane, Queensland, Australia
    Nat Genet 41:1173-5. 2009
    ..1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis...
  71. 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...
  72. ncbi Scrambler and yotari disrupt the disabled gene and produce a reeler-like phenotype in mice
    M Sheldon
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 389:730-3. 1997
    ..The similar phenotypes of reeler, scrambler, yotari and mdab1 null mice indicate that Reelin and mDab1 function as signalling molecules that regulate cell positioning in the developing brain...
  73. ncbi Loss of Omi mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant mice
    Julie M Jones
    Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109 0618, USA
    Nature 425:721-7. 2003
    ..The neurodegeneration and juvenile lethality in mnd2 mice result from this defect in mitochondrial Omi protease...
  74. 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...
  75. pmc Crimean-Congo hemorrhagic fever virus glycoprotein processing by the endoprotease SKI-1/S1P is critical for virus infectivity
    Eric Bergeron
    Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector Borne and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
    J Virol 81:13271-6. 2007
    ..SKI-1/S1P may represent a promising antiviral target...
  76. 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...
  77. ncbi Clinical implications of fibroblast activation protein in patients with colon cancer
    Leonard R Henry
    Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111 2497, USA
    Clin Cancer Res 13:1736-41. 2007
    ..The primary objective of this study was to evaluate the clinical significance of stromal FAP in human colon cancers by immunohistochemisty...
  78. ncbi Assembly of adherens junctions is required for sphingosine 1-phosphate-induced matriptase accumulation and activation at mammary epithelial cell-cell contacts
    Ruei Jiun Hung
    Lombardi Cancer Center, Georgetown Univ Medical Center 3970 Reservoir Rd NW, Washington, DC 20057 1412, USA
    Am J Physiol Cell Physiol 286:C1159-69. 2004
    ..The coupling of matriptase activation to adherens junction assembly and actin cytoskeletal rearrangement may serve to ensure tight control of matriptase activity, restricted to cell-cell junctions of mammary epithelial cells...
  79. ncbi HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins
    Chio Oka
    Division of Gene Function in Animals, Nara Institute of Science and Technology, 8916 5 Takayama, Ikoma, Nara 630 0101, Japan
    Development 131:1041-53. 2004
    ..Taken together, these data indicate that HtrA1 protease is a novel inhibitor of Tgfbeta family members...
  80. doi Proteases in bacterial pathogenesis
    Hanne Ingmer
    Department of Veterinary Disease Biology, University of Copenhagen, Faculty of Life Sciences Stigbøjlen 4, University of Copenhagen, Frederiksberg C DK1870, Denmark
    Res Microbiol 160:704-10. 2009
    ..We have focused on the contribution of the conserved Lon, Clp, HtrA and FtsH proteases to pathogenesis and have highlighted common biological processes for which their activities are important for virulence...
  81. 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...
  82. ncbi Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer
    Jianghua Wang
    Department of Pathology, Baylor College of Medicine and Michael E DeBakey Department of Veterans Affairs Medical Center, Houston, TX 77030, USA
    Cancer Res 66:8347-51. 2006
    ..Thus, both the isoforms of TMPRSS2/ERG fusions expressed and expression level may affect prostate cancer progression...
  83. pmc Long-range disruption of gene expression by a selectable marker cassette
    C T Pham
    Washington University School of Medicine, Department of Medicine, St Louis, MO 63110 1093, USA
    Proc Natl Acad Sci U S A 93:13090-5. 1996
    ..These results suggest that the PGK-Neo cassette can interact productively with locus control regions and thereby disrupt normal interactions between local and long-distance regulatory regions within a tissue-specific domain...
  84. pmc Risk- and non-risk-associated variants at the 10q26 AMD locus influence ARMS2 mRNA expression but exclude pathogenic effects due to protein deficiency
    Ulrike Friedrich
    Institute of Human Genetics, University of Regensburg, Franz Josef Strauss Allee 11, 93053 Regensburg, Germany
    Hum Mol Genet 20:1387-99. 2011
    ..Consequently, our data suggest that pathogenic effects due to ARMS2 protein deficiency are unlikely to account for AMD pathology...
  85. 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...
  86. doi Changes in mRNA and protein levels of human HtrA1, HtrA2 and HtrA3 in ovarian cancer
    Joanna Narkiewicz
    Department of Biochemistry, University of Gdansk, Kladki 24, 80 822 Gdansk, Poland
    Clin Biochem 41:561-9. 2008
    ..Expression of human HtrA1, HtrA2, HtrA3 and TGF-beta1 genes was examined in ovarian tissue specimens including 19 normal ovaries, 20 benign tumors, 7 borderline tumors, 44 cancers and 8 Krukenberg tumors...
  87. 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...
  88. pmc Inhibition of mutation and combating the evolution of antibiotic resistance
    Ryan T Cirz
    Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA
    PLoS Biol 3:e176. 2005
    ..Our findings indicate that the inhibition of mutation could serve as a novel therapeutic strategy to combat the evolution of antibiotic resistance...
  89. doi A mechanism for inside-out lamination in the neocortex
    Jonathan A Cooper
    Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Trends Neurosci 31:113-9. 2008
    ..This 'detach and go' model explains many aspects of inside-out lamination, defects in the Reeler mutant and results of recent genetic and in utero experiments...
  90. 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...
  91. doi HtrA proteins as targets in therapy of cancer and other diseases
    Dorota Zurawa-Janicka
    University of Gdansk, Department of Biochemistry, Kladki 24, 80 822 Gdansk, Poland
    Expert Opin Ther Targets 14:665-79. 2010
    ..They are involved in the development and progression of several pathological processes such as cancer, neurodegenerative disorders and arthritic diseases...
  92. doi Genetic variability in the mitochondrial serine protease HTRA2 contributes to risk for Parkinson disease
    Veerle Bogaerts
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Hum Mutat 29:832-40. 2008
    ..The latter underpins a previously unrecognized role for altered HTRA2 expression as a risk factor relevant to parkinsonian neurodegeneration...
  93. pmc Sequence-specific intramembrane proteolysis: identification of a recognition motif in rhomboid substrates
    Kvido Strisovsky
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Mol Cell 36:1048-59. 2009
    ..Our work demonstrates that intramembrane proteases can be sequence specific and that genome-wide substrate prediction based on their recognition motifs is feasible...
  94. ncbi Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations
    S E Hong
    Division of Neurogenetics, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts, USA
    Nat Genet 26:93-6. 2000
    ....
  95. doi Determinants of structural and functional plasticity of a widely conserved protease chaperone complex
    Melisa Merdanovic
    Centre for Medical Biotechnology, FB Biology and Geography, University Duisburg Essen, Essen, Germany
    Nat Struct Mol Biol 17:837-43. 2010
    ..The implications of these data for the mechanism of protein quality control are discussed...
  96. pmc LOC387715/HTRA1 gene polymorphisms and susceptibility to age-related macular degeneration: A HuGE review and meta-analysis
    Yu Tong
    Laboratory of Early Development and Injuries, Center for Research of Child Development and Disease, West China Second University Hospital, Chengdu, China
    Mol Vis 16:1958-81. 2010
    ....
  97. doi Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response
    N Moisoi
    Cell Death Regulation Laboratory, MRC Toxicology Unit, Leicester LE1 9HN, UK
    Cell Death Differ 16:449-64. 2009
    ..We therefore propose that this brain-specific transcriptional response to stress may be important in the advance of neurodegenerative diseases...
  98. 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)...
  99. pmc Reelin promoter hypermethylation in schizophrenia
    Dennis R Grayson
    Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois, 1601 West Taylor Street, Chicago, IL 60612, USA
    Proc Natl Acad Sci U S A 102:9341-6. 2005
    ..Collectively, the data show that this promoter region has positive and negative properties and that the function of this complex cis element relates to its methylation status...
  100. ncbi A cut above the rest: the regulatory function of plant proteases
    Andreas Schaller
    Institute of Plant Physiology and Biotechnology 260, University of Hohenheim, 70593 Stuttgart, Germany
    Planta 220:183-97. 2004
    ..This article reviews recent findings for the major catalytic classes, i.e. the serine, cysteine, aspartic, and metalloproteases, emphasizing the regulatory function of representative enzymes...
  101. ncbi Characterization of matriptase expression in normal human tissues
    Michael D Oberst
    Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA
    J Histochem Cytochem 51:1017-25. 2003
    ..This suggests that although matriptase is broadly expressed among many types of epithelial cells, its activity within a tissue may be regulated in part at the protein and mRNA levels during the differentiation of selected epithelia...

Research Grants65

  1. Serpin Modulation of Inflammatory Vasculitis; Potential for Immunomodulatory Ther
    ALEXANDRA ROSE LUCAS; Fiscal Year: 2010
    ..We have successfully tested one of these serpins, Serp-1, in a small phase 2A clinical trial for anti-inflammatory activity in unstable coronary syndromes (Viron Therapeutics, Inc;proprietary information). ..
  2. Cross-talk Between Coagulation, Inflammation, and Immunity
    Lawrence L Leung; Fiscal Year: 2013
    ..We believe that this crosstalk between blood clotting, inflammation and immunity is important and highly relevant to our understanding of many diseases including cancer, inflammatory diseases, and abnormal blood clotting. ..
  3. Hepcidin-based screening for infantile iron deficiency
    Mark D Fleming; Fiscal Year: 2010
    ....
  4. The Kallikrein/Kinin-Mast Cell Interaction in Volume Overload
    CHIH CHANG KEVIN WEI; Fiscal Year: 2013
    ....
  5. Identification and Analysis of Flavivirus Protease and RNA Helicase Inhibitors
    Radhakrishnan Padmanabhan; Fiscal Year: 2009
    ....
  6. Molecular Mechanisms of Disease Progression in Myeloid Malignancy
    ELIZABETH ANN EKLUND; Fiscal Year: 2013
    ..Targeting these mechanisms may lead to cure in CML by abolishing the CSC/LSC, and suggest therapeutic approaches to other forms of cancer with dysregulation of Fas and bcatenin. ..
  7. Mechanistic Characterization and Genetic Analysis of Systemic Iron Homeostasis
    Xin Du; Fiscal Year: 2011
    ....
  8. Enzymology of Chlamydia Pathogenesis
    Dewey G McCafferty; Fiscal Year: 2013
    ..abstract_text> ..
  9. Prolylcarboxypeptidase is a Risk Factor for Cardiovascular Disease
    Alvin H Schmaier; Fiscal Year: 2013
    ..Up-regulation of PRCP may be a target to protect individuals from cardiovascular disease as manifested by hypertension and arterial thrombosis as seen in stroke and MI. ..
  10. Regulation of NETosis in antibacterial lung defense
    EILEEN REMOLD-O'DONNELL; Fiscal Year: 2013
    ....
  11. Characterizaton of Motility Factor Receptor
    Avraham Raz; Fiscal Year: 2012
    ..It is expected that these studies will lead to a better diagnosis, treatment and development of rational therapy. ..
  12. Clinical trial of self complementary AAV8-mediated gene transfer for hemophilia B
    Andrew M Davidoff; Fiscal Year: 2013
    ..abstract_text> ..
  13. Regulation of Endothelial ICAM-1 and PMN-Mediated Lung Injury by Actin Dynamics
    Fabeha Fazal; Fiscal Year: 2013
    ....
  14. NAPS2 Continuation Genome Wide Association Study of Pancreatitis
    DAVID CLEMENT WHITCOMB; Fiscal Year: 2011
    ..abstract_text> ..
  15. Cell Surface Plasminogen Activation and Hypertension
    Robert J Parmer; Fiscal Year: 2013
    ....
  16. Inflammatory Proteases, Ubiquitin Proteasome System, and Myocyte Death
    Abdelkarim Sabri; Fiscal Year: 2012
    ....
  17. Expression of clp genes in Streptococcus mutans
    Indranil Biswas; Fiscal Year: 2013
    ..Successful completion of our studies could lead to the development of novel therapeutic treatments to reduce tooth decay. ..
  18. Structure and function analysis of C1/C1q and MBL using a novel peptide inhibitor
    NEEL KUMAR KRISHNA; Fiscal Year: 2012
    ....
  19. Effect of Macrolide Treatment on a Novel Pathway of Neutrophilic Inflammation in
    J Edwin Blalock; Fiscal Year: 2010
    ..If successful, the current proposal will yield fundamental insights into the disease process and a new and specific biomarker for COPD as well as suggesting new therapeutic targets. (End of Abstract) ..
  20. Tick feeding regulation by orthologous tick saliva serine protease inhibitors
    Albert Mulenga; Fiscal Year: 2013
    ..scapularis native tick saliva serpins in tick feeding regulation. To validate tick immunity and anamnestic antibody response to tick infestation of white tailed deer immunized with recombinant tick saliva serpin antigens. ..
  21. PLASMINOGEN AND PLASMIN: STRUCTURE AND FUNCTION
    Francis J Castellino; Fiscal Year: 2013
    ..This wil alow the establishment of new paradigms for treatment of diseases associated with these infections. ..
  22. Plasminogen activator inhibitor-1 in tumor progression and metastasis
    Yves A DeClerck; Fiscal Year: 2013
    ....
  23. Novel Protective Antiapoptotic Action of Alpha 1-Antitrypsin In Emphysema
    Rubin M Tuder; Fiscal Year: 2011
    ..abstract_text> ..
  24. Biomolecular Markers of Renal Allograft Status
    Thangamani Muthukumar; Fiscal Year: 2013
    ..Study specimens (allograft biopsies, urine and blood) will be from kidney transplant recipients enrolled in two-NIH-sponsored studies;R37 AI051652 and U01 AI08446. ..
  25. Nature of mamalian Cutaneous Permeablilty Barrier
    Peter M Elias; Fiscal Year: 2012
    ..apos; ..
  26. ELUCIDATING THE FUNCTION OF MATRIPTASE-ACTIVATED PDGF D IN BONE METASTATIC PROSTA
    ABDO JAMAL NAJY; Fiscal Year: 2012
    ..Concomitantly, we envision our salient contributions leading to the development of novel and targeted therapeutics for prostate cancer in addition to improving the efficacy of existing treatment modalities. ..
  27. The function(s) of serpin-2 in mosquito immunity and physiology
    Kristin Michel; Fiscal Year: 2013
    ..Therefore, the proposed project is relevant to the NIH-NIAID's mission in relation to the understanding and prevention of re-emerging infectious diseases. ..
  28. Role of Fibrinolytic System in Vein Graft Remodeling
    William P Fay; Fiscal Year: 2013
    ..We anticipate that the information gained from our experiments will lead to new strategies to treat and prevent vein graft disease. ..
  29. Pneumococcal capsule and host innate immunity
    Moon H Nahm; Fiscal Year: 2012
    ..Our work would also expand the concept of "serotype" to include serotype specific interactions with innate opsonins, as well as antibodies, and this new concept may bring further innovations in vaccine designs against many pathogens. ..
  30. Serine Protease Corin in Pregnancy-induced Hypertension
    Qingyu Wu; Fiscal Year: 2013
    ..In this study, we will try to understand how corin works and if we can develop new corin-based methods to diagnose and treat high blood pressure during pregnancy. 1 ..
  31. Membrane Receptors Regulating Megakaryocyte Endocytosis of Factor V from Plasma
    BETH BOUCHARD; Fiscal Year: 2012
    ..End of Abstract) ..
  32. Regulation of Pal-1 in Atherosclerosis and Thrombosis
    Yolanda M Fortenberry; Fiscal Year: 2013
    ..This is particularly important, since to date, there are no PAI-1 inhibitors available for clinical use (End of Abstract) ..
  33. Role of Chymase In The Post-Myocardial Infarction Heart
    Ahsan Husain; Fiscal Year: 2013
    ..The proposed identification of the downstream targets of chymase should provide a foundation for the development of novel therapeutic agents directed toward patients with cardiovascular disease. ..
  34. CYTOMEGALOVIRUS DNA REPLICATION AND INVERSION
    Edward S Mocarski; Fiscal Year: 2013
    ..This investigation will lead to a more complete understanding of the interplay of cellular and viral functions as determinants of cell fate. ..
  35. Indolecarbinol target proteins and anti-cancer signaling in human melanoma cells
    Gary L Firestone; Fiscal Year: 2013
    ..Our proposed studies will establish the preclinical foundation that is needed to eventually develop novel and low cost I3C-based therapeutic strategies for human skin cancers. ..
  36. HTS Approach to Correction of Alpha-1-Antitrypsin Misfolding Disease
    William Balch; Fiscal Year: 2009
    ..We propose to use our HTS technologies to screen large chemical libraries provided by the MLCPN to identify biologically active compounds that will prevent the disease phenotype. ..
  37. Identification of serine hydrolases involved in Plasmodium host cell invasion
    Brooke Anderson-White; Fiscal Year: 2013
    ..There is an urgent need for novel malaria therapeutics and the results of this research could lead directly to the development of these drugs. ..
  38. Pathogen specific imaging of endocarditis
    PETER ROLF PANIZZI; Fiscal Year: 2013
    ..Agent development will focus on clinical feasibility to address the aforementioned urgent medical needs, with the ultimate goal of using PET/MRI detection of bacteria in valve lesions for the diagnosis of acute endocarditis in patients. ..
  39. Sex-Dependent PTHrP Processing and Lung Cancer Survival
    Randolph H Hastings; Fiscal Year: 2013
    ..This goal may be close to fruition because we have found individual cyclic guanidine compounds , a class of molecule with known effects on serine protease activity, that reduce amino PTHrP in lung cancer. ..
  40. PDGF D AND PROSTATE CANCER BONE METASTASIS
    Hyeong Reh Choi Kim; Fiscal Year: 2013
    ....
  41. Real-time imaging of tPA fluorescent hybrids in hippocampal neurons
    Janis E Lochner; Fiscal Year: 2011
    ..tPA-mediated extracellular proteolysis is also implicated in excitotoxic cell death and the neuronal degeneration associated with Alzheimer<s disease. ..
  42. Thrombin Mediated Cytotoxicity during Cerebral Ischemia
    Patrick D Lyden; Fiscal Year: 2013
    ....
  43. Role of HCV p7 and NS2 in infectious virus production
    Charles M Rice; Fiscal Year: 2012
    ..The resulting findings should aid development of more effective treatments aimed at eradicating this deadly viral disease. ..
  44. A Protective Role for Fibroblast Activation Protein (FAP) in Pulmonary Fibrosis
    Ming Hui Fan; Fiscal Year: 2013
    ..Dr. Fan's project will determine the mechanism(s) by which FAP protects against the development of pulmonary fibrosis after lung injury. ..
  45. A novel diagnostic biomarker for hepatocellular carcinoma and cholangiocarcinoma
    Xuanyong Lu; Fiscal Year: 2012
    ....
  46. Inflammatory Effect of Enteric Bacterial-Mediated Intestinal Permeability
    IAN MICHAEL CARROLL; Fiscal Year: 2013
    ..Additionally, the proposed research is innovative in our opinion as it will allow for the design of rational pathophysiology-directed probiotic treatment of GI disease. ..
  47. Anti-Inflammatory mechanisms of soybean-derived Bowman-Birk protease inhibitor
    Abdolmohamad Rostami; Fiscal Year: 2012
    ..We believe that these studies will provide in depth insights into anti-inflammatory actions of BBI, and facilitate its use as a supplementary treatment for inflammatory diseases. ..
  48. Serpin Regulation of Coagulation Proteases
    Alireza R Rezaie; Fiscal Year: 2013
    ....
  49. PROTEINASE SYSTEMS IN INSECT HEMOLYMPH
    Michael R Kanost; Fiscal Year: 2013
    ..sexta system for fundamental studies on the regulation of serine protease activity. ..
  50. Molecular Mechanism of Severe Congenital Neutropenia
    H Grimes; Fiscal Year: 2009
    ..More generally, this work should impact our understanding of hematopoiesis, as well as engender greater understanding of GFI1 function. ..
  51. Functional Studies of Kallikrein 4
    James P Simmer; Fiscal Year: 2013
    ..We expect to prove that Klk4 aggressively cleaves enamel proteins during the maturation stage of amelogenesis and that this function is essential for the proper maturation of enamel crystals. ..
  52. Mechanisms linking the hemostatic protease thrombin to arthritic disease
    Matthew J Flick; Fiscal Year: 2013
    ....
  53. Characterization of a novel AB5 cytotoxin
    Adrienne W Paton; Fiscal Year: 2011
    ..This will provide a foundation for the future development of countermeasures including therapeutic agents and vaccines. ..
  54. GLUCOCORTICOSTEROID ACTION IN INFLAMMATORY DISEASE
    Robert P Schleimer; Fiscal Year: 2013
    ..Our successful completion of the aims described in this proposal will yield valuable new insight into the mechanisms of glucocorticoid action in human disease. ..
  55. Exploration of novel pan-HPV treatments to block development of AIDS-associated c
    Wijbe Martin Kast; Fiscal Year: 2010
    ....
  56. Matrix remodeling in tumor growth and metastasis in a murine breast cancer model
    Lisa L Chang; Fiscal Year: 2011
    ..Further, our studies may lead to an early breast cancer diagnostic biomarker that could be used in the clinic to save time, resources and most importantly, life. ! ..
  57. Identification of Novel Genes That Modulate Systemic Iron Homeostasis
    KARIN ELISABETH FINBERG; Fiscal Year: 2013
    ..It is hoped that this work will lead to new treatments for both inherited and acquired iron disorders and to the development of new clinical tests that can predict prognosis and guide therapy in these disorders. ..
  58. 2012 New Insights into Coagulation
    Eleanor Pollak; Fiscal Year: 2012
    ..The main focus of the conference revolves around the innovation of new oral anticoagulants that have been FDA approved within the last two years. ..
  59. Mechanisms of Deregulation of Matriptase in Breast Cancer
    Chen Yong Lin; Fiscal Year: 2013
    ....
  60. Transcriptional Coregulation in Pancreatic Adenocarcinoma Progression
    MARK JAKOB FERREIRA; Fiscal Year: 2013
    ....
  61. Determining Molecular and Cellular Mechanisms of Glaucoma
    KAYARAT SAIDAS NAIR; Fiscal Year: 2013
    ..Second, employ a proteome-wide strategy named terminal amine isotopic labeling of substrates (TAILS) to identify PRSS56 substrates. I will validate the in vivo specificity of these interactions using molecular approaches. ..
  62. Serine Proteinase Inhibitors (Serpins) in Tick Feeding and Physiology
    Albert Mulenga; Fiscal Year: 2009
    ..Identification of important tick proteins that regulate tick physiology and facilitate tick feeding is important before alternative tick control methods can be developed. ..
  63. Investigation of protein interactions in intrinsic blood coagulation pathway
    Divi Venkateswarlu; Fiscal Year: 2007
    ..A and B patient mutational database and the proposed structural models, and if yes, can one use the protein-protein interaction data at the atomic details to engineer the therapeutic proteins? [unreadable] [unreadable] [unreadable]..
  64. Dengue and West Nile Viral Protease Inhibitors
    Radhakrishnan Padmanabhan; Fiscal Year: 2005
    ..Since there is no effective vaccine available for either DEN or WNV, this antiviral strategy is likely to yield lead inhibitors useful as therapeutic agents in the control of these lethal pathogens. ..
  65. STRUCTURE BASED ANALYSIS OF DENGUE VIRUS SERINE PROTEASE
    Krishna Murthy; Fiscal Year: 2004
    ..It will also permit a structural definition of alternate targets for inhibition of the protease and their detailed evaluation. ..