endopeptidases

Summary

Summary: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.

Top Publications

  1. pmc Defining the human deubiquitinating enzyme interaction landscape
    Mathew E Sowa
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 138:389-403. 2009
  2. pmc Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes
    Francisca E Reyes-Turcu
    Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Annu Rev Biochem 78:363-97. 2009
  3. ncbi Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE
    R Vassar
    Amgen, Inc, One Amgen Center Drive, M S 29 2 B, Thousand Oaks, CA 91320 1799, USA
    Science 286:735-41. 1999
  4. ncbi Breaking the chains: structure and function of the deubiquitinases
    David Komander
    Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
    Nat Rev Mol Cell Biol 10:550-63. 2009
  5. ncbi A genomic and functional inventory of deubiquitinating enzymes
    Sebastian M B Nijman
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cell 123:773-86. 2005
  6. pmc Mechanisms, regulation and consequences of protein SUMOylation
    Kevin A Wilkinson
    Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U K
    Biochem J 428:133-45. 2010
  7. ncbi The differential modulation of USP activity by internal regulatory domains, interactors and eight ubiquitin chain types
    Alex C Faesen
    Division of Biochemistry and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Chem Biol 18:1550-61. 2011
  8. ncbi Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome
    Rati Verma
    Department of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA
    Science 298:611-5. 2002
  9. ncbi DUBA: a deubiquitinase that regulates type I interferon production
    Nobuhiko Kayagaki
    Department of Physiological Chemistry, Genentech, South San Francisco, CA 94080, USA
    Science 318:1628-32. 2007
  10. ncbi Tobacco etch virus protease: mechanism of autolysis and rational design of stable mutants with wild-type catalytic proficiency
    R B Kapust
    Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, PO Box B, Frederick, MD 21702-1201, USA
    Protein Eng 14:993-1000. 2001

Detail Information

Publications330 found, 100 shown here

  1. pmc Defining the human deubiquitinating enzyme interaction landscape
    Mathew E Sowa
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Cell 138:389-403. 2009
    ....
  2. pmc Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes
    Francisca E Reyes-Turcu
    Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Annu Rev Biochem 78:363-97. 2009
    ..This review discusses ubiquitin-specific DUBs, some of the generalizations emerging from recent studies of the regulation of DUB activity, and their roles in various cellular processes...
  3. ncbi Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE
    R Vassar
    Amgen, Inc, One Amgen Center Drive, M S 29 2 B, Thousand Oaks, CA 91320 1799, USA
    Science 286:735-41. 1999
    ..Finally, the expression pattern and subcellular localization of BACE were consistent with that expected for beta-secretase. Future development of BACE inhibitors may prove beneficial for the treatment of Alzheimer's disease...
  4. ncbi Breaking the chains: structure and function of the deubiquitinases
    David Komander
    Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
    Nat Rev Mol Cell Biol 10:550-63. 2009
    ..Due to their wide-ranging involvement in key regulatory processes, these enzymes might provide new therapeutic targets...
  5. ncbi A genomic and functional inventory of deubiquitinating enzymes
    Sebastian M B Nijman
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cell 123:773-86. 2005
    ..In addition, we review the literature concerning these enzymes, with particular emphasis on their function, specificity, and the regulation of their activity...
  6. pmc Mechanisms, regulation and consequences of protein SUMOylation
    Kevin A Wilkinson
    Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U K
    Biochem J 428:133-45. 2010
    ..In the present review, we briefly describe the SUMOylation pathway and present an overview of the recent findings that are beginning to identify some of the mechanisms that regulate protein SUMOylation...
  7. ncbi The differential modulation of USP activity by internal regulatory domains, interactors and eight ubiquitin chain types
    Alex C Faesen
    Division of Biochemistry and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Chem Biol 18:1550-61. 2011
    ..USPs can hydrolyze all linkages and show modest Ub-chain preferences, although some show a lack of activity toward linear di-Ub. This comprehensive kinetic analysis highlights the variability within the USP family...
  8. ncbi Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome
    Rati Verma
    Department of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA
    Science 298:611-5. 2002
    ..Our findings reveal an unexpected coupling between substrate deubiquitination and degradation and suggest a unifying rationale for the presence of the lid in eukaryotic proteasomes...
  9. ncbi DUBA: a deubiquitinase that regulates type I interferon production
    Nobuhiko Kayagaki
    Department of Physiological Chemistry, Genentech, South San Francisco, CA 94080, USA
    Science 318:1628-32. 2007
    ..A discrete ubiquitin interaction motif within DUBA was required for efficient deubiquitination of TRAF3 and optimal suppression of IFN-I. Our data identify DUBA as a negative regulator of innate immune responses...
  10. ncbi Tobacco etch virus protease: mechanism of autolysis and rational design of stable mutants with wild-type catalytic proficiency
    R B Kapust
    Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, PO Box B, Frederick, MD 21702-1201, USA
    Protein Eng 14:993-1000. 2001
    ..One of the P1' mutants, S219V, was not only far more stable than the wild-type protease (approximately 100-fold), but also a more efficient catalyst...
  11. ncbi Deubiquitinases in cancer: new functions and therapeutic options
    J M Fraile
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Oviedo, Spain
    Oncogene 31:2373-88. 2012
    ..Further understanding of these processes may provide answers to multiple remaining questions on DUB functions and lead to the development of DUB-targeting strategies to expand the repertoire of molecular therapies against cancer...
  12. ncbi Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease
    Hiroaki Fukumoto
    Alzheimer Disease Research Unit, Center for Aging, Genetics, and Neurodegeneration, Massachusetts General Hospital East, Bldg 114, Room 2010, 114 16th Street, Charlestown, MA 02129, USA
    Arch Neurol 59:1381-9. 2002
    ....
  13. pmc Deubiquitinases as a signaling target of oxidative stress
    Xiomaris M Cotto-Rios
    Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Cell Rep 2:1475-84. 2012
    ..We propose that DUBs of the cysteine protease family act as ROS sensors in human cells and that ROS-mediated DUB inactivation is a critical mechanism for fine-tuning stress-activated signaling pathways...
  14. pmc Bacteriophage endolysins: a novel anti-infective to control Gram-positive pathogens
    Vincent A Fischetti
    Laboratory of Bacterial Pathogenesis, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Int J Med Microbiol 300:357-62. 2010
    ..Here we review the current literature showing the effectiveness of these enzymes in controlling a variety of infections...
  15. ncbi Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization
    Muyang Li
    Institute for Cancer Genetics, and Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, New York 10032, USA
    Nature 416:648-53. 2002
    ..These findings reveal an important mechanism by which p53 can be stabilized by direct deubiquitination and also imply that HAUSP might function as a tumour suppressor in vivo through the stabilization of p53...
  16. ncbi Increased expression of the amyloid precursor beta-secretase in Alzheimer's disease
    R M Damian Holsinger
    Department of Pathology, Mental Health Research Institute, The University of Melbourne, Parkville, Victoria 3010, Australia
    Ann Neurol 51:783-6. 2002
    ..Similarly, we found the levels of the amyloid precursor protein C-terminal fragment produced by beta-secretase to be increased by nearly twofold in Alzheimer's disease cortex...
  17. ncbi A dynamic role of HAUSP in the p53-Mdm2 pathway
    Muyang Li
    Institute for Cancer Genetics and Department of Pathology, College of Physicians and Surgeons, Columbia University, 1150 St Nicholas Avenue, New York, NY 10032, USA
    Mol Cell 13:879-86. 2004
    ..This study provides an example of an ubiquitin ligase (Mdm2) that is directly regulated by a deubiquitinase (HAUSP) and also reveals a dynamic role of HAUSP in the p53-Mdm2 pathway...
  18. ncbi Endolysins as antimicrobials
    Daniel C Nelson
    Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, USA
    Adv Virus Res 83:299-365. 2012
    ..To put phage endolysin work in a broader context, this chapter includes relevant studies of other well-characterized PG hydrolase antimicrobials...
  19. ncbi Regulation of monoubiquitinated PCNA by DUB autocleavage
    Tony T Huang
    Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Nat Cell Biol 8:339-47. 2006
    ..Our results define a regulatory mechanism for protein ubiquitination that involves the signal-induced degradation of an inhibitory DUB...
  20. ncbi Disjunction of homologous chromosomes in meiosis I depends on proteolytic cleavage of the meiotic cohesin Rec8 by separin
    S B Buonomo
    Research Institute of Molecular Pathology, University of Vienna, Austria
    Cell 103:387-98. 2000
    ..We show here that cleavage of Rec8 by separin at one of two different sites is necessary for the resolution of chiasmata and the disjunction of homologous chromosomes during meiosis...
  21. pmc Protein partners of deubiquitinating enzymes
    Karen H Ventii
    Department of Biochemistry, Rollins Research Building, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Biochem J 414:161-75. 2008
    ..In the present review we suggest that, like ligases, much of the regulation and specificity of deubiquitination arises from the association of DUBs with these protein partners...
  22. ncbi Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis
    Vaibhav Kapuria
    Division of Hematology Oncology, Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109, USA
    Cancer Res 70:9265-76. 2010
    ..Our results show that chemical modification of a previously described JAK2 inhibitor results in the unexpected discovery of a novel DUB inhibitor with a unique antitumor mechanism...
  23. ncbi The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis
    Elena Rivkin
    Samuel Lunenfeld Research Institute, Mt Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada
    Nature 498:318-24. 2013
    ..This work provides support for the biological importance of linear (de)ubiquitination in angiogenesis, craniofacial and neural development and in modulating Wnt signalling...
  24. ncbi Small ubiquitin-related modifier (SUMO)-specific proteases: profiling the specificities and activities of human SENPs
    Jowita Mikolajczyk
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 282:26217-24. 2007
    ..Using these synthetic substrates we reveal that the SUMO domain enhances catalysis of SENP1, -2, -5, -6, and -7, demonstrating substrate-induced activation of SENPs by SUMOs...
  25. ncbi Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis
    H Zou
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Science 285:418-22. 1999
    ..The oncogenic nature of increased expression of vSecurin may result from chromosome gain or loss, produced by errors in chromatid separation...
  26. pmc Regulation of NF-κB by deubiquitinases
    Edward W Harhaj
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, FL, USA
    Immunol Rev 246:107-24. 2012
    ..Deubiquitinases and the ubiquitin/proteasome components that regulate NF-κB may serve as novel therapeutic targets for inflammatory diseases and cancer...
  27. ncbi An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase to anaphase transition in yeast
    R Ciosk
    Research Institute of Molecular Pathology, Vienna, Austria
    Cell 93:1067-76. 1998
    ..We propose that the APC promotes sister separation not by destroying cohesins but instead by liberating the "sister-separating" Esp1 protein from its inhibitor Pds1p...
  28. ncbi Chemistry-based functional proteomics reveals novel members of the deubiquitinating enzyme family
    Anna Borodovsky
    Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Chem Biol 9:1149-59. 2002
    ..We show that this polypeptide reacts with the C terminus of Ub, thus demonstrating DUB-like enzymatic activity for this novel superfamily of proteases...
  29. ncbi Bacteriophage lytic enzymes: novel anti-infectives
    Vincent A Fischetti
    Laboratory of Bacterial Pathogenesis, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Trends Microbiol 13:491-6. 2005
    ..Thus, lysins could be an effective anti-infective in an age of mounting antibiotic resistance...
  30. ncbi Neprilysin degrades both amyloid beta peptides 1-40 and 1-42 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases
    K Shirotani
    Laboratory for Proteolytic Neuroscience, Brain Science Institute, RIKEN, 2 1 Hirosawa, Wako Shi, Saitama 351 0198, Japan
    J Biol Chem 276:21895-901. 2001
    ..We expressed NEP, phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PEX), NEPLPs, and damage-induced neuronal endopeptidase (DINE) in 293 cells as 95- to 125-..
  31. ncbi Identification of a novel aspartic protease (Asp 2) as beta-secretase
    I Hussain
    Department of Neurosciences, SmithKline Beecham Pharmaceuticals, Harlow, Essex, United Kingdom
    Mol Cell Neurosci 14:419-27. 1999
    ..Asp 2 localizes to the Golgi/endoplasmic reticulum in transfected cells and shows clear colocalization with APP in cells stably expressing the 751-amino-acid isoform of APP...
  32. ncbi Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein
    B De Strooper
    Experimental Genetics Group, Flemish Institute for Biotechnology VIB4, Center for Human Genetics, K U Leuven, Belgium
    Nature 391:387-90. 1998
    ..Our results indicate that mutations in PS1 that manifest clinically cause a gain of function and that inhibition of PS1 activity is a potential target for anti-amyloidogenic therapy in Alzheimer's disease...
  33. ncbi Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde
    Min Hu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA
    Cell 111:1041-54. 2002
    ..Binding by ubiquitin aldehyde induces a drastic conformational change in the active site that realigns the catalytic triad residues for catalysis...
  34. ncbi A cryptic protease couples deubiquitination and degradation by the proteasome
    Tingting Yao
    Department of Biochemistry, University of Iowa, 51 Newton Road, Iowa City, Iowa 52242, USA
    Nature 419:403-7. 2002
    ..The inability to remove ubiquitin can be rate-limiting for degradation in vitro and is lethal to yeast. Unlike all other known deubiquitinating enzymes (DUBs) that are cysteine proteases, POH1 appears to be a Zn(2+)-dependent protease...
  35. pmc Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne
    Anja Bremm
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nat Struct Mol Biol 17:939-47. 2010
    ..Our data highlight the intrinsic specificity of the ubiquitin system that extends to Lys11-linked chains and emphasize that differentially linked polyubiquitin chains must be regarded as independent post-translational modifications...
  36. pmc Suppression of cancer cell growth by promoting cyclin D1 degradation
    Jing Shan
    Institute for Cancer Genetics and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 1130 St Nicholas Avenue, New York, NY 10032, USA
    Mol Cell 36:469-76. 2009
    ..These findings suggest that targeting USP2 is an effective approach to induce growth suppression in the cancer cells addicted to cyclin D1 expression...
  37. ncbi Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases
    Victor Quesada
    Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, Spain
    Biochem Biophys Res Commun 314:54-62. 2004
    ....
  38. ncbi Bacteriophage endolysins--current state of research and applications
    Martin J Loessner
    Institute of Food Science and Nutrition, Swiss Federal Institute of Technology ETH, Schmelzbergstrasse 7, CH 8092 Zurich, Switzerland
    Curr Opin Microbiol 8:480-7. 2005
    ..Clearly, phage endolysins represent great tools for use in molecular biology, biotechnology and in medicine, and we are just beginning to tap this potential...
  39. ncbi The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway
    Sebastian M B Nijman
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Cell 17:331-9. 2005
    ..We propose that USP1 deubiquitinates FANCD2 when cells exit S phase or recommence cycling after a DNA damage insult and may play a critical role in the FA pathway by recycling FANCD2...
  40. pmc The otubain YOD1 is a deubiquitinating enzyme that associates with p97 to facilitate protein dislocation from the ER
    Robert Ernst
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA
    Mol Cell 36:28-38. 2009
    ..The assignment of a p97-associated ubiquitin processing function to YOD1 adds to our understanding of p97's role in the dislocation process...
  41. pmc VHL protein-interacting deubiquitinating enzyme 2 deubiquitinates and stabilizes HIF-1alpha
    Zaibo Li
    Department of Urology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642, USA
    EMBO Rep 6:373-8. 2005
    ....
  42. pmc The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2
    Lauren F Stevenson
    CR UK Cell Transformation Research Group, Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
    EMBO J 26:976-86. 2007
    ..Our data identify the deubiquitinating enzyme USP2a as a novel regulator of the p53 pathway that acts through its ability to selectively target Mdm2...
  43. ncbi The P1' specificity of tobacco etch virus protease
    Rachel B Kapust
    Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, P O Box B, Frederick, MD 21702, USA
    Biochem Biophys Res Commun 294:949-55. 2002
    ..The results indicate that many side-chains can be accommodated in the P1' position of a TEV protease recognition site with little impact on the efficiency of processing...
  44. ncbi A UAF1-containing multisubunit protein complex regulates the Fanconi anemia pathway
    Martin A Cohn
    Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 28:786-97. 2007
    ..Taken together, our results describe a mechanism of regulation of the deubiquitinating enzyme, USP1, and of DNA repair...
  45. ncbi DUBs and cancer: the role of deubiquitinating enzymes as oncogenes, non-oncogenes and tumor suppressors
    Sajjad Hussain
    Division of Pediatric Hematology Oncology, Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Cell Cycle 8:1688-97. 2009
    ..Given the numbers of ubiquitin-dependent pathways where we do not yet understand the role of deubiquitination, it is certain that the list of cancer-related DUBs will grow in coming years...
  46. pmc Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein
    X Lin
    Protein Studies Program, Oklahoma Medical Research Foundation, and Department of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
    Proc Natl Acad Sci U S A 97:1456-60. 2000
    ..Alignment of cleavage site sequences of peptides indicates that the specificity of memapsin 2 resides mainly at the S(1)' subsite, which prefers small side chains such as Ala, Ser, and Asp...
  47. pmc Targeting of a chlamydial protease impedes intracellular bacterial growth
    Jan G Christian
    Institute for Medical Microbiology, Immunology and Hygiene, Technische Universitat Munchen, Munich, Germany
    PLoS Pathog 7:e1002283. 2011
    ..These results define CPAF as the first protein that is essential for replication of Chlamydia. We suggest that this role makes CPAF a potential anti-infective therapeutic target...
  48. ncbi Muralytic activity and modular structure of the endolysins of Pseudomonas aeruginosa bacteriophages phiKZ and EL
    Yves Briers
    Division of Gene Technology, Department of Biosystems, Katholieke Universiteit Leuven, Kasteelpark Arenberg 21, B 3001 Leuven, Belgium
    Mol Microbiol 65:1334-44. 2007
    ..Both KZ144 and EL188 appear to be a natural chimeric enzyme, originating from a recombination of a cell wall-binding domain encoded by a Bacillus or Clostridium species and a catalytic domain of an unknown ancestor...
  49. ncbi USP1 deubiquitinates ID proteins to preserve a mesenchymal stem cell program in osteosarcoma
    Samuel A Williams
    Department of Physiological Chemistry, Genentech, Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Cell 146:918-30. 2011
    ..Our observations implicate USP1 in preservation of the stem cell state that characterizes osteosarcoma and identify USP1 as a target for differentiation therapy...
  50. pmc Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains
    David Komander
    Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    EMBO Rep 10:466-73. 2009
    ..Our results highlight remarkable specificity determinants within the ubiquitin system...
  51. pmc The deubiquitinating enzyme USP-46 negatively regulates the degradation of glutamate receptors to control their abundance in the ventral nerve cord of Caenorhabditis elegans
    Jennifer R Kowalski
    Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA 02111, USA
    J Neurosci 31:1341-54. 2011
    ..This work suggests that the balance between the addition and removal of ubiquitin is important for glutamate receptor trafficking...
  52. ncbi NF-kappaB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling
    Karine Enesa
    British Heart Foundation Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London W12 ONN, United Kingdom
    J Biol Chem 283:7036-45. 2008
    ..Thus we conclude that Cezanne forms a novel negative feedback loop in pro-inflammatory signaling and that it suppresses NF-kappaB activation by targeting RIP1 signaling intermediaries for deubiquitination...
  53. ncbi The Drosophila developmental gene fat facets has a human homologue in Xp11.4 which escapes X-inactivation and has related sequences on Yq11.2
    M H Jones
    University of Cambridge, Department of Pathology, UK
    Hum Mol Genet 5:1695-701. 1996
    ....
  54. pmc Cdc48 and Ufd3, new partners of the ubiquitin protease Ubp3, are required for ribophagy
    Batool Ossareh-Nazari
    Institut Jacques Monod, Universite Paris VII, CNRS, Batiment Buffon, 15 Rue Hélène Brion, Paris 75205, France
    EMBO Rep 11:548-54. 2010
    ..By contrast, proteasome-dependent degradation does not participate in this process. Our data favour the idea that these factors cooperate to recognize and deubiquitinate specific substrates of ribophagy before their vacuolar degradation...
  55. ncbi Dual inhibition of sister chromatid separation at metaphase
    O Stemmann
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 107:715-26. 2001
    ..We propose that separase activation at the metaphase-anaphase transition requires the removal of both securin and an inhibitory phosphate...
  56. pmc Identification of a chlamydial protease-like activity factor responsible for the degradation of host transcription factors
    G Zhong
    Department of Microbiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA
    J Exp Med 193:935-42. 2001
    ..Thus, CPAF represents a unique secreted protein produced by an obligate intracellular bacterial pathogen to interfere with effective host adaptive immunity...
  57. ncbi A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains
    J M Zapata
    Burnham Institute, La Jolla, California 92037, USA
    J Biol Chem 276:24242-52. 2001
    ..We propose the moniker TEFs (TD-encompassing factors) for this large family of proteins...
  58. ncbi Taking aim on bacterial pathogens: from phage therapy to enzybiotics
    Juan A Hermoso
    Grupo de Cristalografia Macromolecular y Biologia Estructural, Instituto Quimica Fisica Rocasolano, CSIC, Serrano 119, 28006 Madrid, Spain
    Curr Opin Microbiol 10:461-72. 2007
    ..These results allow endolysins to be considered as effective antimicrobials with potentially important applications in medicine and biotechnology...
  59. ncbi Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests
    Shigeru Tomida
    Division of Biomodeling, Graduate School of Bioagricultural Sciences, Nagoya University, Furo cho, Chikusa ku, Nagoya, Japan
    Nat Genet 41:688-95. 2009
    ..These phenotypes were rescued in transgenic mice with bacterial artificial chromosomes containing wild-type Usp46. Thus, Usp46 affects the immobility in the TST and FST, and it is implicated in the regulation of GABA action...
  60. ncbi Ras-GAP SH3 domain binding protein (G3BP) is a modulator of USP10, a novel human ubiquitin specific protease
    C Soncini
    European Institute of Oncology, Department of Experimental Oncology, Via Ripamonti 435, 20141 Milan, Italy
    Oncogene 20:3869-79. 2001
    ..The USP10/G3BP complex appears to co-immunoprecipitate with ubiquitinated species that could be substrates of USP10...
  61. ncbi Engineered diubiquitin synthesis reveals Lys29-isopeptide specificity of an OTU deubiquitinase
    Satpal Virdee
    Medical Research Council Laboratory of Molecular Biology, Cambridge, England, United Kingdom
    Nat Chem Biol 6:750-7. 2010
    ..Moreover, we profile a panel containing 10% of the known human deubiquitinases on Lys6- and Lys29-linked ubiquitin and discover that TRABID cleaves the Lys29 linkage 40-fold more efficiently than the Lys63 linkage...
  62. pmc Human ELG1 regulates the level of ubiquitinated proliferating cell nuclear antigen (PCNA) through Its interactions with PCNA and USP1
    Kyoo Young Lee
    Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 285:10362-9. 2010
    ..Taken together, ELG1 specifically directs USP1-UAF1 complex for PCNA deubiquitination...
  63. ncbi Emerging roles of deubiquitinases in cancer-associated pathways
    Joseph J Sacco
    Physiological Laboratory, School of Biomedical Sciences, University of Liverpool, Liverpool, L69 3BX, UK
    IUBMB Life 62:140-57. 2010
    ..We review the current literature that associates DUBs with cancer and discuss their suitability as drug targets of the future...
  64. ncbi Structural basis and specificity of human otubain 1-mediated deubiquitination
    Mariola J Edelmann
    Henry Wellcome Building for Molecular Physiology, Department of Clinical Medicine, University of Oxford, Roosevelt Drive, Oxford OX37BN, UK
    Biochem J 418:379-90. 2009
    ....
  65. ncbi USP15 is a deubiquitylating enzyme for receptor-activated SMADs
    Masafumi Inui
    Department of Medical Biotechnologies, Section of Histology and Embryology, University of Padua, Viale G Colombo 3, 35100 Padua, Italy
    Nat Cell Biol 13:1368-75. 2011
    ..As such, USP15 is critical for the occupancy of endogenous target promoters by the SMAD complex. These data identify an additional layer of control by which the ubiquitin system regulates TGFβ biology...
  66. ncbi Phages will out: strategies of host cell lysis
    I Young
    Dept of Biochemistry and Biophysics, Texas A and M University, College Station, TX 77843 2128, USA
    Trends Microbiol 8:120-8. 2000
    ..By contrast, lytic single-stranded RNA and DNA phages accomplish lysis by producing a single lysis protein without muralytic activity...
  67. ncbi A global survey of CRM1-dependent nuclear export sequences in the human deubiquitinase family
    Iraia García-Santisteban
    Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country UPV EHU, B Sarriena s n, 48940 Leioa, Spain
    Biochem J 441:209-17. 2012
    ..Using site-directed mutagenesis, we show that one of these motifs mediates USP21 nuclear export, whereas the second motif is not functional in the context of full-length USP21...
  68. pmc Direct and indirect control of mitogen-activated protein kinase pathway-associated components, BRAP/IMP E3 ubiquitin ligase and CRAF/RAF1 kinase, by the deubiquitylating enzyme USP15
    Sebastian D Hayes
    Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3BX, United Kingdom
    J Biol Chem 287:43007-18. 2012
    ....
  69. pmc Enhanced SUMOylation and SENP-1 protein levels following oxygen and glucose deprivation in neurones
    Helena Cimarosti
    MRC Centre for Synaptic Plasticity, School of Biochemistry, University of Bristol, University Walk, Bristol, UK
    J Cereb Blood Flow Metab 32:17-22. 2012
    ..Taken together, these results suggest a neuroprotective role for neuronal SUMOylation after OGD...
  70. pmc The regulatory particle of the Saccharomyces cerevisiae proteasome
    M H Glickman
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell Biol 18:3149-62. 1998
    ..Overall, regulatory particles from yeasts and mammals are remarkably similar, suggesting that the specific mechanistic features of the proteasome have been closely conserved over the course of evolution...
  71. pmc Two distinct sites in Nup153 mediate interaction with the SUMO proteases SENP1 and SENP2
    Kin Hoe Chow
    Department of Oncological Sciences, University of Utah, Salt Lake City, UT, USA
    Nucleus 3:349-58. 2012
    ..While SENP1 and SENP2 share many characteristics, we show here that SENP1 levels are influenced by the presence of Nup153, whereas SENP2 is not sensitive to changes in Nup153 abundance...
  72. pmc Inactivation of murine Usp1 results in genomic instability and a Fanconi anemia phenotype
    Jung Min Kim
    Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Dev Cell 16:314-20. 2009
    ..Our results indicate that mouse Usp1 functions downstream in the FA pathway. Deubiquitination is a critical event required for Fancd2 nuclear foci assembly, release from chromatin, and function in DNA repair...
  73. ncbi Bacteriophage endolysins as a novel class of antibacterial agents
    Jan Borysowski
    Department of Clinical Immunology, Institute of Transplantology, The Medical University of Warsaw, 02 006 Warsaw, Poland
    Exp Biol Med (Maywood) 231:366-77. 2006
    ..Additionally, we outline current knowledge regarding the structure and natural function of the enzymes in phage biology, including the most recent findings...
  74. pmc The USP1/UAF1 complex promotes double-strand break repair through homologous recombination
    Junko Murai
    Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Mol Cell Biol 31:2462-9. 2011
    ..Disruption of NHEJ in UAF1-deficient cells restored cellular resistance to camptothecin and the PARP inhibitor. Our results indicate that the USP1/UAF1 complex promotes HR, at least in part by suppressing NHEJ...
  75. ncbi P-27/HP endolysin as antibacterial agent for antibiotic resistant Staphylococcus aureus of human infections
    Ragini Gupta
    Division of Biological Standardization, Indian Veterinary Research Institute, Izatnagar, 243122, Uttar Pradesh, India
    Curr Microbiol 63:39-45. 2011
    ..aureus 27/HP challenge infection. Thus, P-27/HP endolysin offers suitable substitute of antibiotics to control S. aureus infections...
  76. ncbi Improved solubility of TEV protease by directed evolution
    Susanne van den Berg
    Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE 171 77 Stockholm, Sweden
    J Biotechnol 121:291-8. 2006
    ..We identified a mutant, TEV(SH), in which three amino acid substitutions result in a five-fold increase in the yield of purified protease with retained activity...
  77. ncbi Identification and characterization of the metal ion-dependent L-alanoyl-D-glutamate peptidase encoded by bacteriophage T5
    Galina V Mikoulinskaia
    Branch of Shemyakin and Ovchinnikov s Institute of Bioorganic Chemistry RAS, Pushchino, Moscow, Russia
    FEBS J 276:7329-42. 2009
    ..The article discusses how an enzyme with such substrate specificity could be fixed in the process of evolution...
  78. pmc The Chlamydia protease CPAF regulates host and bacterial proteins to maintain pathogen vacuole integrity and promote virulence
    Ine Jorgensen
    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA
    Cell Host Microbe 10:21-32. 2011
    ..Thus, CPAF functions in niche protection, inclusion integrity and pathogen survival, making the development of CPAF-specific protease inhibitors an attractive antichlamydial therapeutic strategy...
  79. pmc Role of desumoylation in the development of prostate cancer
    Jinke Cheng
    Department of Cardiology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Neoplasia 8:667-76. 2006
    ..Collectively, these studies indicate that overexpression of SENP1 is associated with prostate cancer development...
  80. ncbi A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain
    B De Strooper
    Neuronal Cell Biology and Gene Transfer Laboratory, Flanders Institute for Biotechnology VIB4, Center for Human Genetics, KU Leuven, Belgium
    Nature 398:518-22. 1999
    ..Thus the targeting of gamma-secretase for the treatment of Alzheimer's disease may risk toxicity caused by reduced Notch signalling...
  81. ncbi Purification and cloning of amyloid precursor protein beta-secretase from human brain
    S Sinha
    Elan Pharmaceuticals, South San Francisco, California 94080, USA
    Nature 402:537-40. 1999
    ..Cloning and expression of the enzyme reveals that human brain beta-secretase is a new membrane-bound aspartic proteinase...
  82. ncbi Control of cell fate by a deubiquitinating enzyme encoded by the fat facets gene
    Y Huang
    Department of Zoology, University of Texas, Austin 78712, USA
    Science 270:1828-31. 1995
    ..Flies bearing fat facets gene mutations were used to show that a Ubp is cell type--and substrate-specific and a regulator of cell fate decisions in a multicellular organism...
  83. ncbi Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity
    R Yan
    Cell and Molecular Biology, Pharmacia and Upjohn, Inc, Kalamazoo, MI 49007, USA
    Nature 402:533-7. 1999
    ..Thus, Asp2 is a new protein target for drugs that are designed to block the production of amyloid beta-peptide peptide and the consequent formation of amyloid plaque in Alzheimer's disease...
  84. pmc APC/CCdh1-dependent proteolysis of USP1 regulates the response to UV-mediated DNA damage
    Xiomaris M Cotto-Rios
    Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA
    J Cell Biol 194:177-86. 2011
    ..Thus, we propose a role for APC/C(Cdh1) in modulating the status of PCNA monoubiquitination and UV DNA repair before S phase entry...
  85. ncbi Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2
    Erik Meulmeester
    Department of Molecular and Cell Biology, Leiden University Medical Center, P O Box 9503, 2300 RA Leiden, The Netherlands
    Mol Cell 18:565-76. 2005
    ..Importantly, impaired deubiquitination of Hdmx/Hdm2 by HAUSP contributes to the DNA damage-induced degradation of Hdmx and transient instability of Hdm2...
  86. pmc Genetic and biochemical characterization of the cell wall hydrolase activity of the major secreted protein of Lactobacillus rhamnosus GG
    Ingmar J J Claes
    Centre of Microbial and Plant Genetics, K U Leuven, Leuven, Belgium
    PLoS ONE 7:e31588. 2012
    ..Immunofluorescence microscopy and the failure to construct a knock-out mutant suggest an indispensable role for Msp2 in priming septum formation in LGG...
  87. pmc Enhanced protein expression in the baculovirus/insect cell system using engineered SUMO fusions
    Li Liu
    LifeSensors, Inc, Research and Development, Malvern, PA 19355, USA
    Protein Expr Purif 62:21-8. 2008
    ..The SUMOstar system will make significant impact in difficult-to-express proteins and especially to those proteins that require the native N-terminal residue for function...
  88. pmc De-ubiquitinating protease USP2a targets RIP1 and TRAF2 to mediate cell death by TNF
    A L Mahul-Mellier
    Imperial College London, Experimental Medicine and Toxicology, Hammersmith Campus, Du Cane Road, Burlington Danes Building, London W12 0NN, UK
    Cell Death Differ 19:891-9. 2012
    ..Consequently, downregulation of USP2a promotes NF-κB activation and protects cells against TNF-induced cell death...
  89. pmc The de-ubiquitinylating enzyme, USP2, is associated with the circadian clockwork and regulates its sensitivity to light
    Heather Dehlin Scoma
    Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America
    PLoS ONE 6:e25382. 2011
    ..Rhythmic expression of USP2 in the SCN and other tissues offers a new level of control of the clock machinery through de-ubiqutinylation and suggests a role for USP2 during circadian adaptation to environmental day length changes...
  90. pmc Blockade of endothelinergic receptors prevents development of proliferative vitreoretinopathy in mice
    María Iribarne
    Facultad de Ciencias Biomedicas, Universidad Austral, Pilar, Buenos Aires, Argentina
    Am J Pathol 172:1030-42. 2008
    ..In addition, the presence of ET-1 and ETR-B in human fibrous membranes suggests that similar treatments could be helpful after PVR has been established...
  91. pmc USP18-based negative feedback control is induced by type I and type III interferons and specifically inactivates interferon α response
    Véronique François-Newton
    Institut Pasteur, Cytokine Signaling Unit, Centre National de la Recherche Scientifique, Unité de Recherche Associée 1961, Paris, France
    PLoS ONE 6:e22200. 2011
    ..This cross-talk could shed light on the reported genetic variation in the IFN λ loci, which has been associated with persistence of hepatitis C virus and patient's response to IFN α2 therapy...
  92. ncbi Mice lacking the USP2 deubiquitinating enzyme have severe male subfertility associated with defects in fertilization and sperm motility
    Nathalie Bedard
    Polypeptide Laboratory, Department of Medicine, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
    Biol Reprod 85:594-604. 2011
    ..We demonstrate for the first time, using mouse transgenic approaches, a role for the ubiquitin system in fertilization...
  93. pmc A specific protein substrate for a deubiquitinating enzyme: Liquid facets is the substrate of Fat facets
    Xin Chen
    Section of Molecular Cell and Developmental Biology, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA
    Genes Dev 16:289-94. 2002
    ..The results show definitively that Lqf is the key substrate of Faf in the eye; Lqf concentration is Faf-dependent, Lqf is ubiquitinated in vivo and deubiquitinated by Faf, and Lqf and Faf interact physically...
  94. pmc The ER-resident ubiquitin-specific protease 19 participates in the UPR and rescues ERAD substrates
    Gerco C Hassink
    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
    EMBO Rep 10:755-61. 2009
    ..Thus, USP19 is the first example of a membrane-anchored DUB involved in the turnover of ERAD substrates...
  95. ncbi Characterization of a chromosomally encoded glycylglycine endopeptidase of Staphylococcus aureus
    L Ramadurai
    Department of Biological Sciences, Illinois State University, Normal 61790 4120, USA
    Microbiology 145:801-8. 1999
    ..Atomic absorption spectrometric analysis of LytM revealed the presence of 0.9 mol zinc (mol LytM)(-1)...
  96. ncbi GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides
    Christopher J Phiel
    Department of Medicine, Division of Hematology Oncology and Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Philadelphia 19104 6148, USA
    Nature 423:435-9. 2003
    ....
  97. pmc Selective and cell-active inhibitors of the USP1/ UAF1 deubiquitinase complex reverse cisplatin resistance in non-small cell lung cancer cells
    Junjun Chen
    Department of Chemistry and Biochemistry, 214A Drake Hall, University of Delaware, Newark, DE 19716, USA
    Chem Biol 18:1390-400. 2011
    ..Our results support USP1/UAF1 as a potential therapeutic target and provide an example of targeting the USP/WD40 repeat protein complex for inhibitor discovery...
  98. ncbi Cell wall-targeting domain of glycylglycine endopeptidase distinguishes among peptidoglycan cross-bridges
    Jeff Zhiqiang Lu
    Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, USA
    J Biol Chem 281:549-58. 2006
    ..Truncation of the highly conserved first 9 N-terminal residues results in loss of specificity to S. aureus cell wall-targeting, suggesting that these residues confer specificity to S. aureus cell wall...
  99. ncbi The bifunctional peptidoglycan lysin of Streptococcus agalactiae bacteriophage B30
    David G Pritchard
    Department of Biochemistry and Molecular Genetics, MCLM 552, 1530 3rd Ave S, University of Alabama at Birmingham, Birmingham, AL 35294 0005, USA
    Microbiology 150:2079-87. 2004
    ..Site-directed mutagenesis of conserved cysteine and histidine residues in the CHAP domain and conserved aspartate and glutamate residues in the Acm domain confirmed their importance for lysozyme and endopeptidase activity respectively...
  100. pmc Take five--BACE and the gamma-secretase quartet conduct Alzheimer's amyloid beta-peptide generation
    Christian Haass
    Department of Biochemistry, Adolf Butenandt Institute, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, Munchen, Germany
    EMBO J 23:483-8. 2004
    ..It now appears that one needs to Take Five genes to produce a deadly peptide by a proteolytic mechanism, which paradoxically is otherwise of pivotal importance for development and cell fate decisions...
  101. ncbi The therapeutic potential of deubiquitinating enzyme inhibitors
    Frederic Colland
    Hybrigenics SA, 3 5 Impasse Reille, 75014 Paris, France
    Biochem Soc Trans 38:137-43. 2010
    ..Advances in small molecule-based inhibitors specifically targeting DUBs are presented in this review...

Research Grants63

  1. Heat shock proteins in brain ischemia and stroke
    Midori A Yenari; Fiscal Year: 2013
    ..Recent work in the field has implicated matrix metalloproteinases (MMPs), a family of Zn-dependent endopeptidases, in the breakdown of the extracellular matrix and BBB leading to brain edema and hemorrhage...
  2. Calpain Activates Intracellular TGF-beta1 in Pulmonary Hypertension
    Yunchao Su; Fiscal Year: 2013
    ..Calpain is a family of calcium-dependent non-lysosomal neutral cysteine endopeptidases that act via limited proteolysis of substrate proteins in mammalian cells including pulmonary vascular cells...
  3. Protease regulation of ovarian recrudescence
    KELLY ANSLEY YOUNG; Fiscal Year: 2013
    ..is dependent upon tissue remodeling events, many of which are associated with a family of Zn+dependent endopeptidases, the matrix metalloproteinases (MMPs)...
  4. The role of metalloprotease-PAR1 signaling in vascular injury and repair
    KARYN MARIE AUSTIN; Fiscal Year: 2013
    ..Matrix metalloproteases (MMPs) are a family of endopeptidases that are largely responsible for the degradation of extracellular matrix, and play important roles in vascular ..
  5. Intervention of Disease by Selective Gelatinase Inhibitors
    Shahriar Mobashery; Fiscal Year: 2011
    ..Evidence has shown that members of the matrix metalloproteinase (MMP) family of zinc-dependent endopeptidases, of which 26 are known, play key roles in these processes...
  6. Enzymes involved in neuropeptide biosynthesis and regulation
    Lakshmi A Devi; Fiscal Year: 2013
    ..of cases this occurs by proteolysis of the precursors at 'classical'cleavage sites involving endopeptidases of the subtilisin family...
  7. Role and regulation of Metalloproteinase-9 in the intestine
    Didier Merlin; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): The Metalloproteinases (MMP) are a family of Zn-dependent endopeptidases involved in a variety of physiological and pathological processes that require extracellular matrix degradation or proteolytic ..
  8. ACTIVATION OF COLLAGENASE IN RHEUMATOID ARTHRITIS
    L Windsor; Fiscal Year: 2001
    ..The MMPs are zinc-dependent endopeptidases that are capable of degrading most of the components of the extracellular matrix...
  9. 92K-GL (MMP 9) AND THE INVASIVE PHENOTYPE
    MARTIN BODDEN; Fiscal Year: 1999
    ..92K-GL is a member of the family of matrix metalloproteinases (MMP), a homologous group of 10 zinc dependent endopeptidases which collectively cleave most components of the extracellular matrix (ECM) and basement membrane (BM)...
  10. Multiplexed, Single Molecule Protein Identification for Single Cell Proteomics
    PETER ALAN SIMS; Fiscal Year: 2013
    ..By applying amino acid-specific labels and monitoring the activity of amino acid-specific endopeptidases, single molecule fluorescence imaging can be used to obtain sufficient sequence information from individual ..
  11. LYSOSOMAL PROTEASES OF SPERMATOZOA
    JOHN MC DONALD; Fiscal Year: 1993
    ..intended to establish the biochemical properties and functional significance of new lysosomal-type protease (endopeptidases and exopeptidases) recently detected in guinea pig epididymal spermatozoa...
  12. TARGET-GUIDED BOTULINUM NEUROTOXIN INHIBITOR DISCOVERY
    Hartmuth Kolb; Fiscal Year: 2006
    ..They are zinc endopeptidases that cleave a group of proteins integral to neurotransmitter release, causing flaccid paralysis, which may ..
  13. Mouse Models for Celiac Disease
    Detlef Schuppan; Fiscal Year: 2007
    ..degradation of T cell stimulatory gliadin peptides by exogenous bacterial prolyl endopeptidases, 2. inhibition of intestinal tTG activity by tTG-inhibitors, and 3...
  14. CHARACTERIZATION OF PRONASE ENZYMES
    WILLIAM AWAD; Fiscal Year: 1980
    Studies will be continued with Pronase endopeptidases to determine what groups are regulating the pH dependence for activity in the alkaline range...
  15. BRAIN ENDOPEPTIDASES AND NEUROPEPTIDE METABOLISM
    Sherwin Wilk; Fiscal Year: 2001
    ....
  16. PROTEIN CLEAVAGE SITES IN EXPERIMENTAL CATARACTOUS LENSE
    Larry David; Fiscal Year: 1993
    ..Intact lens proteins will then be incubated in vitro with three different major lens endopeptidases (high molecular neutral protease complex, trypsin-like protease, and calpain II)...
  17. PEPTIDE/PROTEIN ANALYSIS FACILITY
    C Kahn; Fiscal Year: 1991
    ..Moreover, the facility is essential for the identification, immunological analysis and cloning of (1) endopeptidases responsible for processing proinsulin, (2) substrates of the insulin and insulin-like growth factor I receptor ..
  18. IgA Protease Therapy of IgA Nephropathy in Animal Models
    Andrew Plaut; Fiscal Year: 2007
    ..These enzymes are endopeptidases produced by bacteria (Streptococcus, Neisseria, Haemophilus, and Clostridium species), and irrespective of ..
  19. Targeting Matrix Metalloproteinases for Tumor Imaging
    Carolyn Anderson; Fiscal Year: 2004
    ..Metalloproteinases (MMPs) are a family of over 20 types of enzymes, both secreted and membrane-bound zinc endopeptidases, which collectively are capable of degrading all the components of the extracellular matrix...
  20. OVARY-SELECTIVE KNOCKOUT OF IGF-I
    Eli Adashi; Fiscal Year: 2004
    ..with a ligand (IGF-I), a receptor (type I), IGF binding proteins (IGFBPs 4&5) and IGFBP-4 and 5-directed endopeptidases. According to current views, shaped in large measure by numerous in vitro observations, the primary and ..
  21. Diabetic Neuropathy: Implications for Wound Repair
    Nicole Gibran; Fiscal Year: 2006
    ..an excisional wound repair model in hyperglycemic db/db mice, we will replace substance P and inhibit neutral endopeptidases activity. We will also test the effects of antioxidants in this murine wound model. [unreadable] [unreadable]
  22. Prolyl endopeptidases to treat Celiac Sprue
    Jeremy Minshull; Fiscal Year: 2005
    ..Preliminary results have indicated that bacterial prolyl endopeptidases can degrade these peptides and may thus be an effective treatment for celiac patients...
  23. MMP-7 and SNARE Cleavage in Neuroinflammation
    Katherine Conant; Fiscal Year: 2009
    ..important family of proteolytic enzymes is the matrix metalloproteinases (MMPs), zinc- dependent, secreted endopeptidases that can cleave extracellular matrix proteins as well as cytokines and cell surface receptors...
  24. DEVELOPMENT OF INTESTINAL TRANSPORT OF CA++ AND PI
    Fayez Ghishan; Fiscal Year: 2007
    ..phosphate-lib (NaPi-lIb), sodium phosphate-Ill (NaPi-lll), and Phosphate encoding gene with Homologies to Endopeptidases on the X chromosome (PHEX) genes...
  25. Metalloproteinase Functon in Tuberculosis Granulomas
    Angelo Izzo; Fiscal Year: 2004
    ..Matrix metalloproteinases (MMPs) are endopeptidases that degrade the extracellular matrix and have been associated with various pathogenic states...
  26. PROTEIN ANALYSIS BY THERMOSPRAY MASS SPECTROMETRY
    DOUGLAS DYCKES; Fiscal Year: 1990
    ..The mapping procedure will allow rapid analysis of protein samples in terms of their fragmentation by various endopeptidases, the masses of those fragments, and partial sequence data on each fragment...
  27. Structure and mechanism of signal peptide peptidase
    Michael S Wolfe; Fiscal Year: 2010
    ..A structure of SPP would provide tremendous insight into the workings of an unusual new class of enzymes that are critical to both biology and medicine. ..
  28. The Role of Presenilin in Gamma-Secretase Activity
    Michael Wolfe; Fiscal Year: 2009
    ..for substrate-protease recognition? (3) What is the role of Aph-1 and NCT in the assembly and activity of the protease complex? (4) How do mutations in PS that cause familial AD alter the specificity and activity of gamma-secretase? ..
  29. PRESENILIN DOMAINS AND RECONSTITUTION OF CATALYSIS
    Samuel Gandy; Fiscal Year: 2007
    ..This investigation will permit the identification of the minimal functional unit for gamma-secretase activity and potentially support the notion that PS1 is indeed the catalytic component of the gamma-secretase complex. ..
  30. BABAA RECEPTORS IN AGING & ALZHEIMER'S DISEASE
    Samuel Gandy; Fiscal Year: 2002
    ....
  31. PRESENILIN ENDOPROTEASE & GAMMA-SECRETASE ACTIVITY
    Weiming Xia; Fiscal Year: 2003
    ..abstract_text> ..
  32. TRANSMITTER NEUROANATOMY IN ALZHEIMERS DISEASE
    Samuel Gandy; Fiscal Year: 2002
    ....
  33. Estrogen, ACE2 and Salt-Sensitivity
    Mark Chappell; Fiscal Year: 2008
    ..Lewis strain. ..
  34. 900MHz NMR for Structural Biology in Chicago
    PETER GETTINS; Fiscal Year: 2007
    ..As part of the facility, a resource will be established for development of procedures for intein-based segmental isotopic labeling of proteins, as well as for production of segmentally labeled DNA and RNA species. ..
  35. The structural basis for APP cleavability
    Ya Ha; Fiscal Year: 2009
    ..abstract_text> ..
  36. ACQUISITION OF CRYOPROBE FOR 600 MHZ NMR SPECTROMETER
    PETER GETTINS; Fiscal Year: 2001
    ..Olson, with interests in serpin inhibition mechanism, Dr. Patston, with interests in the structure of the serpin angiotensinogen, and Dr. Silver, who is characterizing a unique silver binding protein, silE. ..
  37. Structural examination of serpin-protein interactions
    PETER GETTINS; Fiscal Year: 2009
    ..Dudley Strickland. ..
  38. PATHOGENIC MECHANISMS OF PRESENILIN MUTATION
    Robert Siman; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  39. ULTRASENSITIVE CALORIMETRY SYSTEM FOR BIOMOLECULES
    PETER GETTINS; Fiscal Year: 2001
    ..abstract_text> ..
  40. 3rd Intl Symp on Serpin Biology, Structure and Function
    PETER GETTINS; Fiscal Year: 2002
    ..v) To provide an opportunity for promising junior scientists and minorities to play a major role in the meeting. ..
  41. METALLOPROTEASES IN CONNECTIVE TISSUE MATRIX BREAKDOWN
    Hideaki Nagase; Fiscal Year: 2002
    ..The principal investigator also proposes to examine the role of cell surface TIMP-2 in this activation process. ..
  42. Inhibition of GBS Carriage by Engineered Lactobacilli
    David Pritchard; Fiscal Year: 2004
    ..If successful, this approach might also be used to protect against other genital, oral, and intestinal pathogens, especially those to which no effective mucosal immunity appears to develop. ..
  43. Robotics Extraction System/HPLC for Shared Resource Lab
    Mark Chappell; Fiscal Year: 2005
    ..abstract_text> ..
  44. Discovery of biomarkers of pulmonary hypertension
    Rubin Tuder; Fiscal Year: 2005
    ..abstract_text> ..
  45. B. anthracis Peptidoglycan Deacetylase as a Drug Target
    David Pritchard; Fiscal Year: 2005
    ..anthracis, by inhibiting the deacetylases which specifically render their cell wall peptidoglycans resistant to the action of lysozyme. ..
  46. FUNCTION AND DYSFUNCTION IN HUMAN ANTITHROMBINS
    PETER GETTINS; Fiscal Year: 2007
    ..For antithrombins that have been activated by mutation,[unreadable] x-ray crystallography, through collaboration with Dr. Robin Carrell,[unreadable] will be used.[unreadable]..
  47. Pathogen-specific drug targets for weaponized bacteria
    Vincent Fischetti; Fiscal Year: 2007
    ..In total, these efforts target central virulence factors in critical biowarfare pathogens. ..
  48. The Role of Doa4 in Membrane Protein Trafficking
    Alexander Amerik; Fiscal Year: 2006
    ..3. Proteins necessary for suppression of the doa4 degradation defect by mutations of Vps factors will be identified by mutagenesis, using chemical and genetic approaches. ..
  49. Protein interactions by analytical ultracentrifugation
    PETER GETTINS; Fiscal Year: 2007
    ..The knowledge gained will be invaluable for design of therapeutics against such infections or in amelioration of diseases associated with aberrant functioning of processes such as blood coagulation. [unreadable] [unreadable] [unreadable]..
  50. MEMBRANE TURNOVER AND AMYLOID PRECURSOR PROTEIN RELEASE
    BARBARA SLACK; Fiscal Year: 2001
    ..The proposed experiments will establish the fundamental role of tyrosine kinases in the control of APP processing. ..
  51. Yoga for the Management of HIV-Metabolic Syndromes
    Kevin Yarasheski; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  52. MATRIXINS AND THEIR INHIBITORS IN ANGIOGENESIS
    QING XIANG SANG; Fiscal Year: 2002
    ..The role of each collagen-degrading matrixin in each step of angiogenesis in vitro will be assessed through intervention by the synthetic matrixin inhibitors. ..
  53. EFFECT OF SERINE PROTEASES BY RADIATION IN CNS INJURY
    JASTI RAO; Fiscal Year: 2004
    ..This information in turn should suggest novel targets for therapeutic intervention. ..
  54. Chemical Genetic Analysis of Platelet Granule Secretion
    Robert Flaumenhaft; Fiscal Year: 2008
    ..Once identified, compounds will be tested in a previously established battery of platelet function tests and evaluated for antithrombotic potential in an in vivo murine model of thrombus formation. [unreadable] [unreadable] [unreadable]..
  55. Regulation of the Anaphase-Promoting Complex by the Spindle Checkpoint
    Hongtao Yu; Fiscal Year: 2010
    ..Experiments in this proposal will shed light on the molecular basis of the spindle checkpoint, which might eventually lead to new strategies to treat human cancers. ..
  56. CASPASES, MITOCHONDRIAL FUNCTION AND PARKINSON'S DISEASE
    Anumantha Kanthasamy; Fiscal Year: 2006
    ..abstract_text> ..
  57. Nanoparticle targeting of cathepsin-L inhibitor and doxorubicin in breast cancer
    Shaker Mousa; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  58. Mapping substrate/gamma-secretase interactions
    Raphael Kopan; Fiscal Year: 2009
    ..The genetic approach we propose is based on functional complementation assays;we will also conduct HTS screens in a novel assay directly measuring substrate-enzyme interactions. ..
  59. TRANSMISSION ELECTRON MICROSCOPE
    Martin Katz; Fiscal Year: 2006
    ..Broadening the user base will help make the cost per user of maintaining the instrument as low as possible. [unreadable] [unreadable]..
  60. Serpin Protease Inhibitors & Opioid Neuropeptides
    Vivian Hook; Fiscal Year: 2006
    ..Serpin regulation of opioid peptides that mediate analgesia and stress may lead to development of new therapeutic approaches in pain and neurologic disease. ..