cysteine endopeptidases

Summary

Summary: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22.

Top Publications

  1. ncbi Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
    D W Nicholson
    Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire Dorval, Quebec, Canada
    Nature 376:37-43. 1995
  2. ncbi Protein modification by SUMO
    Erica S Johnson
    Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Annu Rev Biochem 73:355-82. 2004
  3. ncbi The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
    David L Boone
    Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0451, USA
    Nat Immunol 5:1052-60. 2004
  4. ncbi Structure and functions of the 20S and 26S proteasomes
    O Coux
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Biochem 65:801-47. 1996
  5. ncbi Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase
    M Tewari
    Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA
    Cell 81:801-9. 1995
  6. pmc The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway
    T Kirisako
    Department of Cell Biology, National Institute for Basic Biology, Okazaki 444 8585, Japan
    J Cell Biol 151:263-76. 2000
  7. pmc SUMOylation and De-SUMOylation: wrestling with life's processes
    Edward T H Yeh
    Department of Cardiology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 284:8223-7. 2009
  8. pmc Sortases and the art of anchoring proteins to the envelopes of gram-positive bacteria
    Luciano A Marraffini
    Department of Microbiology, Genetics and Cell Biology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA
    Microbiol Mol Biol Rev 70:192-221. 2006
  9. pmc Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes
    Noula Shembade
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, FL 33136, USA
    Science 327:1135-9. 2010
  10. ncbi Cysteine proteases of parasitic organisms
    M Sajid
    Tropical Disease Research Unit, University of California, San Francisco, CA 94122, USA
    Mol Biochem Parasitol 120:1-21. 2002

Detail Information

Publications378 found, 100 shown here

  1. ncbi Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
    D W Nicholson
    Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire Dorval, Quebec, Canada
    Nature 376:37-43. 1995
    ..A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death...
  2. ncbi Protein modification by SUMO
    Erica S Johnson
    Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Annu Rev Biochem 73:355-82. 2004
    ..This review discusses our current understanding of how SUMO conjugation is controlled, as well as the roles of SUMO in a number of biological processes...
  3. ncbi The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
    David L Boone
    Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0451, USA
    Nat Immunol 5:1052-60. 2004
    ..The critical function of this deubiquitinating enzyme in the restriction of TLR signals emphasizes the importance of the regulation of ubiquitin conjugation in innate immune cells...
  4. ncbi Structure and functions of the 20S and 26S proteasomes
    O Coux
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Biochem 65:801-47. 1996
    ..This article focuses on recent progress concerning the biochemical mechanisms and intracellular functions of the 20S and 26S proteasomes...
  5. ncbi Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase
    M Tewari
    Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA
    Cell 81:801-9. 1995
    ..Furthermore, CrmA blocked cleavage of PARP in cells undergoing apoptosis. We propose that Yama may represent an effector component of the mammalian cell death pathway and suggest that CrmA blocks apoptosis by inhibiting Yama...
  6. pmc The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway
    T Kirisako
    Department of Cell Biology, National Institute for Basic Biology, Okazaki 444 8585, Japan
    J Cell Biol 151:263-76. 2000
    ..A reaction similar to ubiquitination is probably involved in the second modification. The reversible modification of Apg8 appears to be coupled to the membrane dynamics of autophagy and the Cvt pathway...
  7. pmc SUMOylation and De-SUMOylation: wrestling with life's processes
    Edward T H Yeh
    Department of Cardiology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 284:8223-7. 2009
    ..This review will focus on the de-SUMOylating enzymes with special attention to their biological function...
  8. pmc Sortases and the art of anchoring proteins to the envelopes of gram-positive bacteria
    Luciano A Marraffini
    Department of Microbiology, Genetics and Cell Biology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA
    Microbiol Mol Biol Rev 70:192-221. 2006
    ..This review focuses on the mechanisms of surface protein anchoring to the cell wall envelope by sortases and the role that these enzymes play in bacterial physiology and pathogenesis...
  9. pmc Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes
    Noula Shembade
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, FL 33136, USA
    Science 327:1135-9. 2010
    ..These findings suggest mechanism of A20 action in the inhibition of inflammatory signaling pathways...
  10. ncbi Cysteine proteases of parasitic organisms
    M Sajid
    Tropical Disease Research Unit, University of California, San Francisco, CA 94122, USA
    Mol Biochem Parasitol 120:1-21. 2002
    ..Cysteine protease classification will be re-examined in light of the diversity uncovered within parasitic organisms...
  11. ncbi Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3
    Guillermo Mariño
    Departamento de Bioquímica y Biología Molecular and Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006 Oviedo, Spain
    J Biol Chem 282:18573-83. 2007
    ..We also propose that this enzyme could play an in vivo role in events associated with tumor progression...
  12. ncbi The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme
    J Yuan
    Program of Neurosciences, Harvard Medical School, Boston, Massachusetts 02115
    Cell 75:641-52. 1993
    ..We propose that the CED-3 protein acts as a cysteine protease in the initiation of programmed cell death in C. elegans and that cysteine proteases also function in programmed cell death in mammals...
  13. pmc The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals
    Osamu Hitotsumatsu
    UCSF Colitis Center, Gastroenterology Division, Department of Medicine, Program in Biomedical Sciences, University of California at San Francisco, San Francisco, CA 94143 0538, USA
    Immunity 28:381-90. 2008
    ..These findings indicate that A20 directly restricts NOD2 induced signals in vitro and in vivo, and provide new insights into how these signals are physiologically restricted...
  14. ncbi Substrate specificities of caspase family proteases
    R V Talanian
    BASF Bioresearch Corp, Worcester, Massachusetts 01605, USA
    J Biol Chem 272:9677-82. 1997
    ..The results also suggest the design of optimal peptidic substrates and inhibitors...
  15. pmc OTUB1 co-opts Lys48-linked ubiquitin recognition to suppress E2 enzyme function
    Yu Chi Juang
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
    Mol Cell 45:384-97. 2012
    ..OTUB1 therefore co-opts Lys48-linked ubiquitin chain recognition to suppress ubiquitin conjugation and the DNA damage response...
  16. ncbi Non-canonical inhibition of DNA damage-dependent ubiquitination by OTUB1
    Shinichiro Nakada
    Center of Integrated Medical Research, School of Medicine, Keio University, 35 Shinano machi, Shinjuku ku, Tokyo, 160 8582, Japan
    Nature 466:941-6. 2010
    ..Finally, OTUB1 depletion mitigates the DSB repair defect associated with defective ATM signalling, indicating that pharmacological targeting of the OTUB1-UBC13 interaction might enhance the DNA damage response...
  17. pmc Lysosomal cysteine proteases: facts and opportunities
    V Turk
    Department of Biochemistry and Molecular Biology, J Stefan Institute, Ljubljana, Slovenia
    EMBO J 20:4629-33. 2001
    ..Some of the features and roles of their structures, specificity, regulation and physiology are discussed...
  18. ncbi Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast
    E Mossessova
    Biochemistry Department, Weill Medical College of Cornell University, New York, New York 10021, USA
    Mol Cell 5:865-76. 2000
    ..Genetic analysis guided by the structure further reveals a regulatory element N-terminal to the proteolytic domain that is required for cell growth in yeast...
  19. ncbi The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B
    V J Palombella
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138
    Cell 78:773-85. 1994
    ..Thus, the ubiquitin-proteasome pathway functions not only in the complete degradation of polypeptides, but also in the regulated processing of precursors into active proteins...
  20. pmc Fungal effector protein AVR2 targets diversifying defense-related cys proteases of tomato
    Mohammed Shabab
    Plant Chemetics Lab, Max Planck Institute for Plant Breeding Research, 50829 Cologne, Germany
    Plant Cell 20:1169-83. 2008
    ..The higher accumulation of PIP1 protein levels compared with RCR3 indicates that PIP1 might be the real virulence target of AVR2 and that RCR3 acts as a decoy for AVR2 perception in plants carrying the Cf-2 resistance gene...
  21. ncbi Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway
    Z Chen
    Myogenics, Inc, Cambridge, Massachusetts 02139, USA
    Genes Dev 9:1586-97. 1995
    ..Thus, ubiquitination provides a mechanistic link between phosphorylation and degradation of I kappa B alpha...
  22. ncbi Gingipains, the major cysteine proteinases and virulence factors of Porphyromonas gingivalis: structure, function and assembly of multidomain protein complexes
    Jan Potempa
    Department of Microbiology, Faculty of Biotechnology, Jagiellonian University, 30 387 Krakow, Poland
    Curr Protein Pept Sci 4:397-407. 2003
    ..This hypothetical scenario is a reasonable explanation for the occurrence of many forms of gingipains...
  23. ncbi A gated channel into the proteasome core particle
    M Groll
    Max Planck Institut fur Biochemie, D 82152 Martinsried, Germany
    Nat Struct Biol 7:1062-7. 2000
    ..Inhibition by the alpha-subunit tails is relieved upon binding of the regulatory particle to the CP to form the proteasome holoenzyme...
  24. ncbi Ubiquitin-dependent protein degradation
    M Hochstrasser
    Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637, USA
    Annu Rev Genet 30:405-39. 1996
    ..This diversity underlies both the high substrate specificity of the ubiquitin system and the variety of regulatory mechanisms that it serves...
  25. ncbi Staphylococcal cysteine protease staphopain B (SspB) induces rapid engulfment of human neutrophils and monocytes by macrophages
    Jan Smagur
    Department of Microbiology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, 30 386 Krakow, Poland
    Biol Chem 390:361-71. 2009
    ..Collectively, this may lead to the depletion of functional neutrophils at the site of infection, thus facilitating staphylococcal colonisation and spreading...
  26. pmc Gingipains from Porphyromonas gingivalis W83 induce cell adhesion molecule cleavage and apoptosis in endothelial cells
    Shaun M Sheets
    Department of Biochemistry and Microbiology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA
    Infect Immun 73:1543-52. 2005
    ..Taken together, these results indicate that gingipains from P. gingivalis can alter cell adhesion molecules and induce endothelial cell death, which could have implications for the pathogenicity of this organism...
  27. 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...
  28. ncbi Human ICE/CED-3 protease nomenclature
    E S Alnemri
    Cell 87:171. 1996
  29. ncbi Crystal structure of human enterovirus 71 3C protease
    Sheng Cui
    State Key Laboratory for Molecular Virology and Genetic Engineering, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, People s Republic of China
    J Mol Biol 408:449-61. 2011
    ..Our data also provides a framework for structure-guided inhibitor design against EV71 3C(pro)...
  30. pmc The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion
    Alida Coppi
    Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010, USA
    J Exp Med 201:27-33. 2005
    ..Inhibitors of CSP processing inhibit cell invasion in vitro, and treatment of mice with E-64, a highly specific cysteine protease inhibitor, completely inhibits sporozoite infectivity in vivo...
  31. ncbi Legumain expression as a prognostic factor in breast cancer patients
    Jessica Gawenda
    Institute of Pathology, Medizinischen Hochschule Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    Breast Cancer Res Treat 102:1-6. 2007
    ..Besides being of prognostic value, legumain might prove to be an important predictive factor in breast cancer, since its unique cleavage specificity is already used in prodrug activation strategies...
  32. pmc Redox regulation of the stability of the SUMO protease SENP3 via interactions with CHIP and Hsp90
    Shan Yan
    Department of Biochemistry and Cell Biology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, PR China
    EMBO J 29:3773-86. 2010
    ..In addition, enhanced SENP3/Hsp90 association is found in cancer. These findings provide new mechanistic insight into how cells regulate the SUMO protease in response to oxidative stress...
  33. ncbi Roles of naturally occurring protease inhibitors in the modulation of host cell signaling and cellular invasion by Trypanosoma cruzi
    Julio Scharfstein
    Lnstituto de Biofisica Carlos Chagas Filho, UFRJ, Rio de Janeiro, Brazil
    Subcell Biochem 47:140-54. 2008
    ..In conclusion, the studies reviewed herein illustrate how regulation of parasite proteases may affect host-parasite equilibrium in the course of IT cruzi infection...
  34. ncbi Identification of Trichomonas vaginalis cysteine proteases that induce apoptosis in human vaginal epithelial cells
    Ulf Sommer
    Mass Spectrometry Resource, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 280:23853-60. 2005
    ..The present results, suggesting that CP-induced programmed cell death may be involved in the pathogenesis of T. vaginalis infection in vivo, may have important implications for therapeutic intervention...
  35. pmc Hemoglobin digestion in blood-feeding ticks: mapping a multipeptidase pathway by functional proteomics
    Martin Horn
    Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 16610 Praha, Czech Republic
    Chem Biol 16:1053-63. 2009
    ..The identified enzymes are potential targets to developing novel anti-tick vaccines...
  36. ncbi Impairment of the ubiquitin-proteasome system by protein aggregation
    N F Bence
    Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA
    Science 292:1552-5. 2001
    ....
  37. ncbi MHC class I expression in mice lacking the proteasome subunit LMP-7
    H J Fehling
    Basel Institute for Immunology, Switzerland
    Science 265:1234-7. 1994
    ..This demonstrates the involvement of LMP-7 in the MHC class I presentation pathway and suggests that LMP-7 functions as an integral part of the peptide supply machinery...
  38. pmc SUMO-specific protease 2 is essential for suppression of polycomb group protein-mediated gene silencing during embryonic development
    Xunlei Kang
    The Department of Biochemistry and Molecular and Cell Biology, The Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Mol Cell 38:191-201. 2010
    ..Our results reveal a critical role for de-SUMOylation in the regulation of PcG target gene expression...
  39. pmc The mechanism of OTUB1-mediated inhibition of ubiquitination
    Reuven Wiener
    Department of Biophysics and Biophysical Chemistry and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nature 483:618-22. 2012
    ..OTUB1 binding also occludes the RING E3 binding site on UBC13, thus providing a further component of inhibition. The general features of the inhibition mechanism explain how OTUB1 inhibits other E2 enzymes in a non-catalytic manner...
  40. ncbi Degradation of elastin by a cysteine proteinase from Staphylococcus aureus
    J Potempa
    Institute of Molecular Biology, Jagiellonian University, Cracow, Poland
    J Biol Chem 263:2664-7. 1988
    ....
  41. 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
    ....
  42. ncbi A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L
    Joris Hemelaar
    Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:51841-50. 2003
    ..The Apg4B/autophagin-1 protease thus serves as a processing/deconjugating enzyme for these four highly divergent mammalian Apg8 homologues...
  43. pmc Host cell invasion by Trypanosoma cruzi is potentiated by activation of bradykinin B(2) receptors
    J Scharfstein
    Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CEP 21990 400 Rio de Janeiro, Brazil
    J Exp Med 192:1289-300. 2000
    ..Analysis of trypomastigote transfectants expressing various cysteine proteinase isoforms showed that invasion competence is linked to the kinin releasing activity of cruzipain, herein proposed as a factor of virulence in Chagas' disease...
  44. ncbi HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubule-associated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates
    Isei Tanida
    Department of Biochemistry, Juntendo University School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo 113 8421, Japan
    J Biol Chem 279:36268-76. 2004
    ..RNA interference of HsAtg4B increased the amount of LC3-PL in HEK293 cells. Taken together, these results suggest that HsAtg4B negatively regulates the localization of LC3 to a membrane compartment by delipidation...
  45. 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...
  46. ncbi Plant proteases: from phenotypes to molecular mechanisms
    Renier A L van der Hoorn
    Plant Chemetics Lab, Max Planck Institute for Plant Breeding Research, Cologne, Germany 50829
    Annu Rev Plant Biol 59:191-223. 2008
    ..Their substrates and activation mechanisms are elusive, however, and represent a challenging topic for further research...
  47. pmc Specific cleavage of the nuclear pore complex protein Nup62 by a viral protease
    Nogi Park
    Department of Basic Medical Sciences, University of Arizona College of Medicine Phoenix, Phoenix, Arizona 85004, USA
    J Biol Chem 285:28796-805. 2010
    ..These results are consistent with a model whereby PV and HRV disrupt nucleo-cytoplasmic trafficking by selectively removing FG repeat domains from a subset of nuclear pore complex proteins...
  48. ncbi A new protease required for cell-cycle progression in yeast
    S J Li
    University of Chicago, Department of Biochemistry and Molecular Biology, Illinois 60637, USA
    Nature 398:246-51. 1999
    ..The pattern of Smt3-coupled proteins in yeast changes markedly throughout the cell cycle, and specific conjugates accumulate in ulp1 mutants. Ulp1 has several functions, including an essential role in the G2/M phase of the cell cycle...
  49. pmc EndoS and SpeB from Streptococcus pyogenes inhibit immunoglobulin-mediated opsonophagocytosis
    Mattias Collin
    Department of Cell and Molecular Biology, Lund University, Sweden
    Infect Immun 70:6646-51. 2002
    ..This suggests that S. pyogenes expresses two enzymes, EndoS and SpeB, which modulate IgG by different mechanisms in order to evade the adaptive immune system...
  50. pmc Structural basis for ubiquitin recognition by the Otu1 ovarian tumor domain protein
    Troy Eugene Messick
    Wistar Institute, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 283:11038-49. 2008
    ..Together, these studies provide new insights into ubiquitin binding and hydrolysis by yeast Otu1 and other OTU domain-containing proteins...
  51. ncbi Comparison of Staphopain A (ScpA) and B (SspB) precursor activation mechanisms reveals unique secretion kinetics of proSspB (Staphopain B), and a different interaction with its cognate Staphostatin, SspC
    Nicholas Nickerson
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, M4N 3M5
    Mol Microbiol 75:161-77. 2010
    ..We conclude that the status of sspBC in S. aureus, as paralogues of the ancestral scpAB genes, facilitated a different activation mechanism, a stable proSspB isoform and modified Staphostatin function...
  52. pmc Immunoproteasome deficiency alters retinal proteasome's response to stress
    Stacy A Hussong
    Department of Ophthalmology, University of Minnesota, Minneapolis, MN, USA
    J Neurochem 113:1481-90. 2010
    ..These results provide key mechanistic insight into novel aspects of proteasome biology and are an important first step in identifying alternative roles for retinal immunoproteasome that are unrelated to its role in the immune response...
  53. ncbi Assembly of pili on the surface of Corynebacterium diphtheriae
    Hung Ton-That
    Committee on Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL 60637, USA
    Mol Microbiol 50:1429-38. 2003
    ..This covalent tethering of adjacent pilin subunits appears to have evolved in many Gram-positive pathogens that encode sortase and pilin subunit genes with sorting signals and pilin motifs...
  54. pmc Otubains: a new family of cysteine proteases in the ubiquitin pathway
    Maxim Y Balakirev
    Departement de Reponse et Dynamique Cellulaires, Commisariat à l Energie Atomique, 17 rue des Martyrs, Grenoble 38054, France
    EMBO Rep 4:517-22. 2003
    ..We have named these proteins otubain 1 and otubain 2, for OTU-domain Ubal-binding protein. Functional analysis of otubains shows that the OTU domain contains an active cysteine protease site...
  55. pmc Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice
    E G Lee
    Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, MC 6084, Chicago, IL 60637, USA
    Science 289:2350-4. 2000
    ..These cells are also more susceptible than control cells to undergo TNF-mediated PCD. Thus, A20 is critical for limiting inflammation by terminating TNF-induced NF-kappaB responses in vivo...
  56. ncbi Immunoproteasome and LMP2 polymorphism in aged and Alzheimer's disease brains
    Michele Mishto
    Department of Experimental Pathology, University of Bologna, 40126 Bologna, Italy
    Neurobiol Aging 27:54-66. 2006
    ....
  57. ncbi Architects at the bacterial surface - sortases and the assembly of pili with isopeptide bonds
    Antoni P A Hendrickx
    Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, Illinois 60637, USA
    Nat Rev Microbiol 9:166-76. 2011
    ..Together, these isopeptide bonds endow these sortase products with adhesive properties and resistance to host proteases...
  58. pmc Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20
    Emre E Turer
    Gastrointestinal Division, Department of Medicine, Biomedical Sciences Program, University of California, San Francisco, San Francisco, CA 94143, USA
    J Exp Med 205:451-64. 2008
    ..These findings provide novel insights into how physiological TLR signals are regulated...
  59. pmc Enterovirus 71 3C protease cleaves a novel target CstF-64 and inhibits cellular polyadenylation
    Kuo Feng Weng
    Research Center for Emerging Viral Infections, Chang Gung University, Kwei Shan Tao Yuan, Taiwan, ROC
    PLoS Pathog 5:e1000593. 2009
    ..This finding is, to our knowledge, the first to demonstrate that a picornavirus protein affects the polyadenylation of host mRNA...
  60. ncbi Cloning, isolation, and characterization of mammalian legumain, an asparaginyl endopeptidase
    J M Chen
    Medical Research Council Peptidase Laboratory, Department of Immunology, The Babraham Institute, Babraham Hall, Babraham, Cambridgeshire CB2 4AT, United Kingdom
    J Biol Chem 272:8090-8. 1997
    ..We discuss the significance of the discovery of a cysteine endopeptidase of a new family and distinctive specificity in man and other mammals...
  61. ncbi Cladosporium Avr2 inhibits tomato Rcr3 protease required for Cf-2-dependent disease resistance
    Henrietta C E Rooney
    Sainsbury Laboratory, John Innes Centre, Norwich NR4 7UH, UK
    Science 308:1783-6. 2005
    ..We show here that Avr2 binds and inhibits Rcr3 and propose that the Rcr3-Avr2 complex enables the Cf-2 protein to activate an HR...
  62. ncbi Procerain, a stable cysteine protease from the latex of Calotropis procera
    Vikash Kumar Dubey
    Molecular Biology Unit, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India
    Phytochemistry 62:1057-71. 2003
    ..Polyclonal antibodies against procerain do not cross-react with other related proteases. Procerain unlike most of the plant cysteine proteases has blocked N-terminal residue...
  63. pmc Regulation of virus-triggered signaling by OTUB1- and OTUB2-mediated deubiquitination of TRAF3 and TRAF6
    Shu Li
    College of Life Sciences, Modern Virology Center, Wuhan University, Wuhan 430072, China
    J Biol Chem 285:4291-7. 2010
    ..These findings suggest that OTUB1 and OTUB2 negatively regulate virus-triggered type I IFN induction and cellular antiviral response by deubiquitinating TRAF3 and -6...
  64. ncbi Infection with enterovirus 71 or expression of its 2A protease induces apoptotic cell death
    Rei Lin Kuo
    Institute of Microbiology and Immunology, School of Life Science, National Yang Ming University, Taipei 112, Taiwan
    J Gen Virol 83:1367-76. 2002
    ..This study added one more example to the growing list of human viruses that induce apoptosis by a virus-encoded protein...
  65. ncbi Assembly of pili in Gram-positive bacteria
    Hung Ton-That
    Committee on Microbiology, University of Chicago, 920 East 58th Street, Chicago, Illinois 60637, USA
    Trends Microbiol 12:228-34. 2004
  66. ncbi A Yersinia effector and a Pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis
    Feng Shao
    Department of Biological Chemistry, Medical School and Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell 109:575-88. 2002
    ..These findings provide new insights into mechanisms of animal and plant pathogenesis...
  67. ncbi Functions of propeptide parts in cysteine proteases
    Bernd Wiederanders
    Institute of Biochemistry, Klinikum, Friedrich Schiller University Jena, Nonnenplan 2, D 07743 Jena, Germany
    Curr Protein Pept Sci 4:309-26. 2003
    ..The function of propeptides of two other important classes of cysteine peptidases - the calpains, clan CA family C4, and the caspases, clan CD family C 14 - are not considered in this review...
  68. ncbi The proteolytic activity of the major dust mite allergen Der p 1 conditions dendritic cells to produce less interleukin-12: allergen-induced Th2 bias determined at the dendritic cell level
    A M Ghaemmaghami
    Division of Molecular and Clinical Immunology, Faculty of Medicine and Health Sciences, University of Nottingham, Queen s Medical Centre, Nottingham, UK
    Clin Exp Allergy 32:1468-75. 2002
    ..Apart from its direct effect on T cells, it is conceivable that the proteolytic activity of Der p 1 may induce the generation of dendritic cells (DCs) that favour a Th2 response...
  69. ncbi Staphylococcus aureus sortase, an enzyme that anchors surface proteins to the cell wall
    S K Mazmanian
    Department of Microbiology and Immunology, UCLA School of Medicine, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA
    Science 285:760-3. 1999
    ..The protein specified by srtA, sortase, may be a useful target for the development of new antimicrobial drugs...
  70. ncbi Anchoring of surface proteins to the cell wall of Staphylococcus aureus. III. Lipid II is an in vivo peptidoglycan substrate for sortase-catalyzed surface protein anchoring
    Adrienne M Perry
    Committee on Microbiology, University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 277:16241-8. 2002
    ....
  71. ncbi Structure of 20S proteasome from yeast at 2.4 A resolution
    M Groll
    Max Planck Institut fur Biochemie, Martinsreid, Germany
    Nature 386:463-71. 1997
    ....
  72. pmc The SUMO protease SENP6 is essential for inner kinetochore assembly
    Debaditya Mukhopadhyay
    Laboratory of Gene Regulation and Development, National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 188:681-92. 2010
    ..Together, these findings reveal a novel mechanism whereby the finely balanced activities of SENP6 and RNF4 control vertebrate kinetochore assembly through SUMO-targeted destabilization of inner plate components...
  73. ncbi Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme
    K Kuida
    Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Science 267:2000-3. 1995
    ..Despite this defect in apoptosis, ICE-/- mice proceed normally through development...
  74. pmc Sortase enzymes in Gram-positive bacteria
    Thomas Spirig
    Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA
    Mol Microbiol 82:1044-59. 2011
    ..We also review recent data that suggest that sortases are targeted to specific sites on the cell surface where they work with other sortases and accessory factors to properly function...
  75. ncbi Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction
    E J Wiertz
    Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 384:432-8. 1996
    ..This process involves the Sec61 complex, in what appears to be a reversal of the reaction by which it translocates nascent chains into the endoplasmic reticulum...
  76. ncbi Protein quality control: U-box-containing E3 ubiquitin ligases join the fold
    Douglas M Cyr
    Dept of Cell and Developmental Biology and The UNC Cystic Fibrosis Center, 524 Taylor Hall, University of North Carolina, Chapel Hill, NC 27599 7060, USA
    Trends Biochem Sci 27:368-75. 2002
    ..These data indicate a model for protein quality control in which the interaction of Hsp70 and Hsp90 with co-chaperones that have either folding or degradatory activity helps to determine the fate of non-native cellular proteins...
  77. ncbi The ubiquitin/26S proteasome pathway, the complex last chapter in the life of many plant proteins
    Richard D Vierstra
    Cellular and Molecular Biology Program, Department of Horticulture, 1575 Linden Drive, University of Wisconsin Madison, Madison, WI 53706, USA
    Trends Plant Sci 8:135-42. 2003
    ..Consequently, it appears that the ubiquitin/26S proteasome pathway rivals transcription complexes and protein kinase cascades as the main player in plant cell regulation...
  78. ncbi ER degradation of a misfolded luminal protein by the cytosolic ubiquitin-proteasome pathway
    M M Hiller
    Institut für Biochemie der Universität Stuttgart, Pfaffenwaldring 55, D 70569 Stuttgart, Germany
    Science 273:1725-8. 1996
    ..It is likely that CPY* entered the ER, was glycosylated, and was then transported back out of the ER lumen to the cytoplasmic side of the organelle, where it was conjugated with ubiquitin and degraded...
  79. pmc The yeast ULP2 (SMT4) gene encodes a novel protease specific for the ubiquitin-like Smt3 protein
    S J Li
    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA
    Mol Cell Biol 20:2367-77. 2000
    ..Our data suggest the existence of a feedback mechanism that limits Smt3-protein ligation when Smt3 deconjugation by both Ulp1 and Ulp2 is compromised, allowing a partial recovery of cell function...
  80. ncbi The mannose receptor mediates the uptake of diverse native allergens by dendritic cells and determines allergen-induced T cell polarization through modulation of IDO activity
    Pierre Joseph Royer
    School of Molecular Medical Sciences, University of Nottingham, Queen s Medical Centre, United Kingdom
    J Immunol 185:1522-31. 2010
    ..In conclusion, our work demonstrates a major role for MR in glycoallergen recognition and in the development of Th2 responses...
  81. ncbi Evolutionary lines of cysteine peptidases
    A J Barrett
    MRC Molecular Enzymology Laboratory, The Babraham Institute, Cambridgeshire, UK
    Biol Chem 382:727-33. 2001
    ..streptopain (C10) and the ubiquitin-specific peptidases (C12, C19), as well as many families of viral cysteine endopeptidases. Clan CD contains the families of clostripain (C11), gingipain R (C25), legumain (C13), caspase-1 (C14) ..
  82. ncbi Cystatin M/E is a high affinity inhibitor of cathepsin V and cathepsin L by a reactive site that is distinct from the legumain-binding site. A novel clue for the role of cystatin M/E in epidermal cornification
    Tsing Cheng
    Department of Dermatology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, P O Box 9101, 6500 HB Nijmegen, The Netherlands
    J Biol Chem 281:15893-9. 2006
    ....
  83. ncbi Gene disruptions demonstrate independent roles for the four falcipain cysteine proteases of Plasmodium falciparum
    Puran S Sijwali
    Department of Medicine, San Francisco General Hospital, University of California San Francisco, CA 94143 0811, USA
    Mol Biochem Parasitol 150:96-106. 2006
    ..Our data suggest key roles for falcipain-2 and falcipain-3 in the development of erythrocytic malaria parasites and a complex interplay between P. falciparum cysteine and aspartic proteases...
  84. ncbi Neuronal induction of the immunoproteasome in Huntington's disease
    Miguel Diaz-Hernandez
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autonoma de Madrid, Contoblanco, 28049 Madrid, Spain
    J Neurosci 23:11653-61. 2003
    ..Our results indicate that LMP2 and LMP7 participate in normal neuronal physiology and suggest a role in HD neurodegeneration...
  85. pmc Two approaches to discovering and developing new drugs for Chagas disease
    J H McKerrow
    Sandler Center at Mission Bay, University of California, San Francisco, CA 94158 2330, USA
    Mem Inst Oswaldo Cruz 104:263-9. 2009
    ..It is optimized for robotic liquid handling and has been validated through a screen of a library of FDA-approved drugs identifying 65 hits...
  86. pmc Caspases: the executioners of apoptosis
    G M Cohen
    MRC Toxicology Unit, University of Leicester, U K
    Biochem J 326:1-16. 1997
    ..Cells undergoing apoptosis following triggering of death receptors execute the death programme by activating a hierarchy of caspases, with caspase-8 and possibly caspase-10 being at or near the apex of this apoptotic cascade...
  87. ncbi P1/HC-Pro, a viral suppressor of RNA silencing, interferes with Arabidopsis development and miRNA unction
    Kristin D Kasschau
    Center for Gene Research and Biotechnology and Department of Botany and Plant Pathology, Oregon State University, Corvallis, OR 97331, USA
    Dev Cell 4:205-17. 2003
    ..The basis for TuMV- and other virus-induced disease in plants may be explained, at least partly, by interference with miRNA-controlled developmental pathways that share components with the antiviral RNA-silencing pathway...
  88. ncbi CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme
    T Fernandes-Alnemri
    Department of Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
    J Biol Chem 269:30761-4. 1994
    ..The apoptotic activity of CPP32 and its high expression in lymphocytes suggest that CPP32 is an important mediator of apoptosis in the immune system...
  89. ncbi Localization of nuclear cathepsin L and its association with disease progression and poor outcome in colorectal cancer
    Shane Sullivan
    Centre for Colorectal Disease, St Vincent s University Hospital, Dublin, Dublin, Ireland
    Int J Cancer 125:54-61. 2009
    ..Moreover, these findings suggest that altering active nuclear Cathepsin L may significantly influence disease progression...
  90. ncbi Immunoproteomics of the active degradome to identify biomarkers for Trichomonas vaginalis
    Lucero A Ramón-Luing
    Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del IPN CINVESTAV IPN, Mexico City, Mexico
    Proteomics 10:435-44. 2010
    ..Purified recombinant CPs were recognized by culture-positive patient sera in 1-D-WB assays. These data show that some CPs could be potential biomarkers for serodiagnosis of trichomonosis...
  91. ncbi A monitoring method for Atg4 activation in living cells using peptide-conjugated polymeric nanoparticles
    Kyung Mi Choi
    Biomedical Research Institute, Korea Institute of Science and Technology, Seongbuk gu, Seoul, South Korea
    Autophagy 7:1052-62. 2011
    ..As our nanoparticles are highly cell-permeable and biocompatible, this detection system has general applicability to living cells and can be extended to cell-based screening to evaluate newly developed compounds...
  92. ncbi Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections
    Jae Hyang Lim
    Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA
    Immunity 27:349-60. 2007
    ..Thus, CYLD is detrimental for host survival, thereby indicating a mechanism underlying the high early mortality of pneumococcal pneumonia...
  93. ncbi Cysteine peptidases in the tomato trypanosomatid Phytomonas serpens: influence of growth conditions, similarities with cruzipain and secretion to the extracellular environment
    Camila G R Elias
    Laboratorio de Estudos Integrados em Bioquimica Microbiana, Departamento de Microbiologia Geral, IMPPG, CCS, Bloco I subsolo, Universidade Federal do Rio de Janeiro UFRJ, Cidade Universitaria, Rio de Janeiro, RJ, Brazil
    Exp Parasitol 120:343-52. 2008
    ..The 40kDa peptidase was also detected in the cell-free culture supernatant, in an active form, which suggests secretion of this peptidase to the extracellular environment...
  94. pmc Enterovirus 71 and coxsackievirus A16 3C proteases: binding to rupintrivir and their substrates and anti-hand, foot, and mouth disease virus drug design
    Guangwen Lu
    Chinese Academy of Sciences, Beijing 100101, China
    J Virol 85:10319-31. 2011
    ..In conclusion, the detailed characterization of both proteases in this study could direct us to a proposal for rational design of EV71/CVA16 3C inhibitors...
  95. ncbi Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme
    S Kumar
    Department of Viral Oncology, Japanese Foundation for Cancer Research, Tokyo
    Genes Dev 8:1613-26. 1994
    ..Our data suggest that Nedd2 is an important component of the mammalian programmed cell death machinery...
  96. ncbi Dual modes of modification of hepatitis A virus 3C protease by a serine-derived beta-lactone: selective crystallization and formation of a functional catalytic triad in the active site
    Jiang Yin
    CIHR Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    J Mol Biol 354:854-71. 2005
    ..The success of soaking IVF into HAV 3C-1a crystals demonstrates the usefulness of this new crystal form in the study of enzyme-inhibitor interactions in the proteolytic active site...
  97. pmc HC-Pro silencing suppressor significantly alters the gene expression profile in tobacco leaves and flowers
    Arto J Soitamo
    Department of Biochemistry and Food Chemistry, Molecular Plant Biology, University of Turku, Vesilinnantie 5, Turku 20014, Finland
    BMC Plant Biol 11:68. 2011
    ..The transcript levels of leaves and flowers of these plants were analysed using microarray techniques (Tobacco 4 × 44 k, Agilent)...
  98. ncbi Insights into cleavage specificity from the crystal structure of foot-and-mouth disease virus 3C protease complexed with a peptide substrate
    Patricia A Zunszain
    Biophysics Section, Blackett Laboratory, Imperial College, Exhibition Road, London SW7 2AZ, UK
    J Mol Biol 395:375-89. 2010
    ..Our results provide a new level of detail in our understanding of the structural basis of polyprotein cleavage by 3C(pro)...
  99. ncbi Loss of lipopolysaccharide receptor CD14 from the surface of human macrophage-like cells mediated by Porphyromonas gingivalis outer membrane vesicles
    Lisa Duncan
    Groupe de Recherche en Ecologie Buccale, Faculte de Medecine Dentaire, Universite Laval, Quebec City, Quebec, Canada G1K 7P4
    Microb Pathog 36:319-25. 2004
    ..Such a phenomenon, which results in an hyporesponsiveness of macrophages to LPS stimulation, may contribute to an increased capacity of P. gingivalis, and other periodontopathogens, to evade the host immune system mechanisms...
  100. ncbi A principal role for the proteasome in endoplasmic reticulum-associated degradation of misfolded intracellular cystic fibrosis transmembrane conductance regulator
    Marina S Gelman
    Department of Biological Sciences, Stanford University, Stanford, California 94305 5020, USA
    J Biol Chem 277:11709-14. 2002
    ..Our results suggest that ubiquitin-proteasome-mediated degradation is the dominant pathway for disposal of misfolded CFTR in mammalian cells and provide new mechanistic insight into endoplasmic reticulum-associated degradation...
  101. pmc Role of Leishmania (Leishmania) chagasi amastigote cysteine protease in intracellular parasite survival: studies by gene disruption and antisense mRNA inhibition
    Vasanthakrishna Mundodi
    Department of Biological Sciences, University of Calgary, Calgary AB T2N1N4, Canada
    BMC Mol Biol 6:3. 2005
    ..chagasi. Here, we have further characterized this cysteine protease gene and demonstrated its role during infection and survival of Leishmania (L.) chagasi within the U937 macrophage cells...

Research Grants67

  1. Right ventricular contractile dysfunction after pressure overload
    CLIFFORD RUSSELL GREYSON; Fiscal Year: 2013
    ..Agents with potential clinical utility will be identified using the isolated papillary muscle model and tested in the pig model. ..
  2. The Role of Adipocyte-Induced Inflammation in Prostate Tumor Progression
    AIMALIE LYNNETTE HARDAWAY; Fiscal Year: 2012
    ..Ultimately, these studies should lead to identification of novel signaling pathways and molecular mechanisms predisposing prostate cells to metastasize to bone. ..
  3. Fic-mediated Adenylylation
    CAROLYN ANN WORBY; Fiscal Year: 2013
    ..This covalent addition of AMP blocks signal transduction pathways in the host that are important for combating bacterial infections. ..
  4. Cell death regulation in proteotoxic therapy
    Wei Xing Zong; Fiscal Year: 2013
    ..At the clinical level, it may establish LC3 or SCCA1 as a molecular signature for suggesting treatment with proteotoxic agents. ..
  5. Cathepsin L in the Biosynthesis of Enkephalins and beta-Endorphin Opioid Peptides
    Steven J Bark; Fiscal Year: 2012
    ....
  6. Molecular mechanisms of pathogen recognition by the Nod-like receptor NLRC4
    Fayyaz S Sutterwala; Fiscal Year: 2012
    ..iii) Determining if NLRC4 recognizes host plasma membrane components following their disruption by bacterial T3SS. ..
  7. K777 for treatment of Chagas Disease: IND-enabling Studies and IND Submission
    Robert Don; Fiscal Year: 2012
    ..This proposal is designed to complete all remaining requirements as agreed with the FDA to allow K777 to move into clinical trials. ..
  8. 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 ..
  9. Cryopyrin/NLRP3 Signaling in Inflammation and Innate Immunity
    Gabriel Nunez; Fiscal Year: 2013
    ..These studies may lead to better understanding of mechanisms that control host defense against human pathogens and the pathogenesis of inflammatory disease. ..
  10. Mechanism of Hepatitis E Virus Replication and Pathogenesis
    Xiang Jin Meng; Fiscal Year: 2013
    ..By completing this project, we expect to identify the viral determinant(s) for HEV host range and pathogenicity and delineate the role of ISG15 in anti-HEV response. ..
  11. Nlrp3 inflammasome signaling in immune responses to Candida albicans
    Fayyaz S Sutterwala; Fiscal Year: 2013
    ..In addition the information gained from the proposed studies will also shed light on the pathogenesis of other fungal organisms. ..
  12. Vaccinia Virus Genetics and Morphogenesis
    Richard C Condit; Fiscal Year: 2013
    ....
  13. Role of a schistosome cysteine protease in Th response polarization
    Stephen J Davies; Fiscal Year: 2013
    ....
  14. Targeting Cathepsin L: A Novel Strategy to Impede Prostate and Breast Cancer Meta
    Dietmar W Siemann; Fiscal Year: 2013
    ....
  15. 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. ..
  16. Impact of CR on inflammasome driven immune-metabolic interactions.
    Vishwa Deep Dixit; Fiscal Year: 2013
    ....
  17. Mechanism and function of a conserved bacterial cyclic-di-GMP receptor system
    Richard B Cooley; Fiscal Year: 2013
    ..Together, this proposal outlines a unique opportunity to reveal the potential of therapeutically targeting this and other c-di-GMP signaling pathways to ameliorate chronic diseases caused by pathogenic bacteria. ..
  18. Characterization of a novel protein required for glomerular podocyte function
    LORI L O'BRIEN; Fiscal Year: 2012
    ..Our research will examine how podocytes form and are maintained, which will facilitate our understanding of what happens to them during disease, and potentially lead to new therapies. ..
  19. Imaging of Cardiac Transplant Rejection
    Matthias Nahrendorf; Fiscal Year: 2013
    ..These longitudinal studies will be used to validate functional macrophage-targeted agents for noninvasive heart transplant imaging. ..
  20. The Role of Inflammasomes in Mucosal Immunity to Intestinal Bacterial Pathogens
    Gabriel Nunez; Fiscal Year: 2013
    ..coli, two enteric bacterial pathogens. These studies may lead to better understanding of mechanisms that control host defense against human pathogens and the pathogenesis of inflammatory disease in the intestine. ..
  21. Functional characterization of Rho inactivation by Vibro cholerae RTX toxin
    BRETT L GEISSLER; Fiscal Year: 2010
    ..The further characterization of components involved in the regulation of Rho GTPases from the proposed research will also benefit eukaryotic cell signaling research. ..
  22. Genetic and Biochemical Study of V. cholerae RTX Toxin
    Karla J F Satchell; Fiscal Year: 2012
    ..Completion of this research will impact not only our understanding of cholera pathogenesis, but also the function of other uncharacterized toxins produced by other human pathogens that share these unique enzymatic activities. ..
  23. Repression of inflammasome by Francisella tularensis
    Meenakshi Malik; Fiscal Year: 2013
    ..This proposal is a step ahead in understanding the immunopathogenesis of tularemia. ..
  24. Chemically Interrogating Clostridium difficile Glucosylating Toxin Activation
    Aimee Shen; Fiscal Year: 2010
    ..By targeting virulence rather than bacterial viability, chemical inhibition of the CPD may reduce the recurrence of antibiotic-induced nosocomial diarrhea. ..
  25. Development of High Throughput Assays for the Hepatitis C Virus NS2 Protease
    Timothy L Tellinghuisen; Fiscal Year: 2013
    ....
  26. Light Activation of Enzyme Inhibition
    JEREMY KODANKO; Fiscal Year: 2013
    ..Literature data confirm that photodynamic therapy is effective against bone tumors in live animal models, which strongly supports our studies. ..
  27. Mechanism and Inhibition of Arginine Deiminase
    Hua Guo; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE The research proposed here is aimed at the elucidation of the catalytic mechanism of arginine deiminase, which may help designing new antibacterial and antiparasitic drugs. ..
  28. Cytomegalovirus Deubiquitinase pUL48: Identifying Substrate and Inhibitors
    D WADE GIBSON; Fiscal Year: 2010
    ..We propose to identify the substrate(s) of this enzyme and identify inhibitors of its activity in high-throughput assays. ..
  29. P. gingivalis Mediated Evasion Strategies
    Caroline A Genco; Fiscal Year: 2013
    ..Successful undertaking of the proposed studies has the potential to identify and validate novel therapeutic interventions that target pathogen evasion mechanisms associated with chronic infection and the resulting inflammatory sequelae. ..
  30. Itch, proteases and protease-activated receptors
    Ethan A Lerner; Fiscal Year: 2013
    ..The results of this project may lead to the development of new drugs to treat itch. ..
  31. Al-2-Dependent Quorum Sensing in the Gram-Positive Bacterium Streptococcus pyogen
    Michael J Federle; Fiscal Year: 2010
    ..The gene encoding the receptor will be cloned and the protein expressed and purified. X-ray crystallography will be used to determine the structure of all or a portion of th'e receptor with and without bound AI-2. ..
  32. Dysregulation of ubiquitination in MALT lymphomas
    Xiaolu Yang; Fiscal Year: 2010
    ....
  33. Controlled expression of a cystatin C-peptide as therapy for Alzheimer's disease
    PHYLLIS ANN SHAW; Fiscal Year: 2012
    ....
  34. Neural Mechanisms of Itch
    ROBERT H LA MOTTE; Fiscal Year: 2013
    ..abstract_text> ..
  35. Chemically Interrogating Clostridium difficile Glucosylating Toxin Activation
    Aimee Shen; Fiscal Year: 2013
    ..Combined with structural methods, the probes will also facilitate analyses of CPD substrate specificity and function, which will in turn inform strategies directed at inhibiting C. difficile glucosylating toxin function. ..
  36. NATURAL IMMUNITY TO ENTAMOEBA HISTOLYTICA
    JONATHAN RAVDIN; Fiscal Year: 1999
    ..This proposal will address an incredibly important issues in amebiasis research and have a major impact on vaccine development and clinical practice in the field. ..
  37. DEGRADABLE HYDROGELS FOR ORAL DELIVERY OF CALCITONIN
    Jindrich Kopecek; Fiscal Year: 2001
    ..Based on in vivo animal data criteria will be studied. Based on in vivo animal data criteria will be established for the design of an oral hCT and CKI delivery system for the treatment of postmenopausal osteoporosis. ..
  38. DEGRADABLE HYDROGELS FOR ORAL DELIVERY OF CALCITONIN
    Jindrich Kopecek; Fiscal Year: 2003
    ..Based on in vivo animal data criteria will be studied. Based on in vivo animal data criteria will be established for the design of an oral hCT and CKI delivery system for the treatment of postmenopausal osteoporosis. ..
  39. A MOLECULAR TOOLKIT FOR SINGLE-MOLECULE PROTEIN SEQUENCING
    James J Havranek; Fiscal Year: 2013
    ..Preliminary results demonstrate that these aims are feasible. Completion of this research will move next-generation protein sequencing much closer to being a reality. ..
  40. CYSTEINE PROTEASES & INHIBITORS IN NEMATODE DEVELOPMENT
    Sara Lustigman; Fiscal Year: 2000
    ..This will provide the basis for developing effective drugs targeting cysteine protease to control onchocerciasis and filariasis in the future. ..
  41. MUCOPOLYSACCHARIDOSES AND CATHEPSIN K
    Dieter Bromme; Fiscal Year: 2007
    ..Altogether, these studies should elucidate the impact of GAGs in MPS on bone resorption catalyzed by cathepsin K. ..
  42. CYSTEINE PROTEASES & INHIBITORS IN NEMATODE DEVELOPMENT
    Sara Lustigman; Fiscal Year: 2005
    ..This will provide the basis for developing effective drugs, targeting cysteine proteases, to control onchocerciasis and filariasis in the future. ..
  43. Mechanistic Dissection of Pheromone-Dependent Regulation of Group A Streptococcal
    Michael J Federle; Fiscal Year: 2013
    ..Demonstration that GAS utilizes Rgg proteins for cell-to-cell signaling will provide a foundation for future development of therapies designed to interfere with intercellular signaling in GAS and in other Rgg-containing organisms. ..
  44. The Role of Cathepsin B and Cystatin C in Alzheimer's Disease
    Li Gan; Fiscal Year: 2013
    ..Confirmation that the CatB-CysC axis action acts in a complementary manner with NEP would lay the foundation for designing effective Abeta clearance strategies. ..
  45. RIGHT VENTRICULAR DYSFUNCTION AFTER PRESSURE OVERLOAD
    Clifford Greyson; Fiscal Year: 2006
    ..abstract_text> ..
  46. DESIGN AND SYNTHESIS OF CYSTEINE PROTEINASE INHIBITORS
    DANIEL RICH; Fiscal Year: 1992
    ..Develop a 3- dimensional model for the human cysteine proteinases, cathepsin B, H, and L, for which X-ray crystal structures are not available...
  47. THE CRES GENE IN REPRODUCTION
    Gail Cornwall; Fiscal Year: 2005
    ..abstract_text> ..
  48. Role of Red Cell Membrane in Malaria Parasite Release
    Manjit Hanspal; Fiscal Year: 2006
    ..Together, the proposed studies on FP-2 may begin to reveal molecular mechanisms underlying the release of malaria parasite from the host erythrocyte. ..
  49. LYSOSOMAL PROTEASES OF SPERMATOZOA
    JOHN MC DONALD; Fiscal Year: 1993
    ....
  50. REGULATION OF INDUCIBLE RAT SALIVARY CYSTATIN
    Gurrinder Bedi; Fiscal Year: 1990
    ..The long term goal of this work is to use the information gained in the rat model as a basis for the study of role of cystatins in normal and pathophysiological conditions...
  51. PROTEASE INHIBITORS IN HUMAN BLADDER CANCER INVASION
    Brian Liu; Fiscal Year: 1993
    ..We will attempt in these studies to determine not only the possible effectiveness of such intervention at a biochemical, cellular, and in vivo level, but also address the fundamental biochemical mechanisms of tumor cell invasion...
  52. DEVELOPMENT OF A VACCINE FOR HUMAN PERIODONTITIS
    ROY PAGE; Fiscal Year: 2001
    ..These observations will contribute in a major way to closing the gaps in our knowledge of the role of the host immune response in the pathogenesis of periodontitis. ..
  53. EOSINOPHIL APOPTOSIS IN ASTHMA
    Gerald Litwack; Fiscal Year: 2001
    ..Furthermore, manipulation of these pathways will be a key area for therapeutic intervention in asthma. ..
  54. REGULATION OF GENE EXPRESSION IN MAMMALIAN CELLS
    Jerry Lingrel; Fiscal Year: 1990
    ..5) To study the role of Alpha1-MAP and kininogens in inflammation. This will be accomplished using an animal model for this response. (6) To determine if a homologous protein to Alpha1-MAP occurs in humans...
  55. MOLECULAR ANALYSIS OF HUMAN SALIVARY CYSTATIN GENES
    Douglas Dickinson; Fiscal Year: 1991
    ..To map the human chromosomal location of the cystatin genes. Information gained through this work will contribute to our understanding of the mechanisms of gene regulation involved in the synthesis of proteins in human salivary glands...
  56. HUMAN PHAGOCYTES, OXYGEN METABOLITES AND INFLAMMATION
    Stephen Weiss; Fiscal Year: 2002
    ....
  57. CHARACTERIZATION OF TUMOR CYSTEINE INHIBITORS
    Bonnie Sloane; Fiscal Year: 1992
    ..Our eventual goal is to interrupt this cascade by designing more effective inhibitors or by altering the expression and subcellular localization of endogenous CPI...
  58. Identifying Calpain-10 Substrates from Human Proteome
    Rihe Liu; Fiscal Year: 2005
    ..abstract_text> ..
  59. A New Class of Serine and Cysteine Protease Inhibitors
    CHRISTOPHER SETO; Fiscal Year: 2006
    ..Finally, the optimized inhibitors will be examined for their ability to inhibit dephosphorylation of the insulin receptor that is catalyzed by PTP1B. ..
  60. Genetic Manipulation of Entamoeba Virulence
    Sharon Reed; Fiscal Year: 2005
    ..These studies should further our understanding of an important virulence factor of E. histolytica and establish the key cysteine proteinases, which are linked to invasion and could be targets of novel drug therapy in the future. ..
  61. Promiscuous and Specific Inhibitors of Cruzain
    Brian Shoichet; Fiscal Year: 2007
    ..We test a rapid method to detect these artifacts, which should significantly advance this critical technique. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  62. Role of cysteine proteases in malaria transmission
    KIM WILLIAMSON; Fiscal Year: 2006
    ..In addition to increasing our understanding of the genes involved, this information can be used to direct the design of cysteine protease inhibitors that will effectively block malaria transmission. ..
  63. PROTEOMICS OF REGULATED EXOCYTOSIS IN OSTEOCLASTS
    F Ross; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  64. Variola Virus G1L:An Antiviral Drug Target
    Dennis Hruby; Fiscal Year: 2005
    ....
  65. LISTERIA PHOSPHOLIPASE ACTIVATION & CELL-TO-CELL SPREAD
    HELENE MARQUIS; Fiscal Year: 2002
    ..monocytogenes spreads from cell to cell. This may provide a novel target for development of drugs to treat or prevent intracellular microbial infections in humans. ..
  66. PROCESSING AND SECRETION OF CATHEPSIN B IN METASTASIS
    ANDREW BAJKOWSKI; Fiscal Year: 1991
    ....
  67. MAST CELL CYSTEINE PROTEASES IN LUNG INFLAMMATION
    Paul Wolters; Fiscal Year: 2003
    ..McKerrow), immunohistopathology (Dr. McDonald), and pulmonary diseases (Dr. Matthay), who will guide the candidates development into an independent investigator in pulmonary research. ..