caspases

Summary

Summary: A family of intracellular CYSTEINE ENDOPEPTIDASES. They play a key role in inflammation and mammalian APOPTOSIS. They are specific for aspartic acid at the P1 position. They are divided into two classes based on the lengths of their N-terminal prodomains. Caspases-1,-2,-4,-5,-8, and -10 have long prodomains and -3,-6,-7,-9 have short prodomains. EC 3.4.22.-.

Top Publications

  1. ncbi The biochemistry of apoptosis
    M O Hengartner
    Cold Spring Harbor Laboratory, New York 11724, USA
    Nature 407:770-6. 2000
  2. ncbi Mitochondria and cell death: outer membrane permeabilization and beyond
    Stephen W G Tait
    Department of Immunology, St Jude Childrens Research Hospital, Memphis, Tennessee 38105, USA
    Nat Rev Mol Cell Biol 11:621-32. 2010
  3. ncbi Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis
    H Li
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 94:491-501. 1998
  4. ncbi The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta
    Fabio Martinon
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Mol Cell 10:417-26. 2002
  5. ncbi Non-canonical inflammasome activation targets caspase-11
    Nobuhiko Kayagaki
    Department of Physiological Chemistry, Genentech Inc, South San Francisco, California 94080, USA
    Nature 479:117-21. 2011
  6. ncbi Apoptosis: controlled demolition at the cellular level
    Rebecca C Taylor
    Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland
    Nat Rev Mol Cell Biol 9:231-41. 2008
  7. ncbi The Bcl2 family: regulators of the cellular life-or-death switch
    Suzanne Cory
    The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria 3050, Australia
    Nat Rev Cancer 2:647-56. 2002
  8. ncbi Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta
    T Nakagawa
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 403:98-103. 2000
  9. pmc Inhibition of macroautophagy triggers apoptosis
    Patricia Boya
    CNRS UMR 8125, Institut Gustave Roussy, Pavillon de Recherche 1, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    Mol Cell Biol 25:1025-40. 2005
  10. 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

Detail Information

Publications334 found, 100 shown here

  1. ncbi The biochemistry of apoptosis
    M O Hengartner
    Cold Spring Harbor Laboratory, New York 11724, USA
    Nature 407:770-6. 2000
    ..Here I review the basic components of the death machinery, describe how they interact to regulate apoptosis in a coordinated manner, and discuss the main pathways that are used to activate cell death...
  2. ncbi Mitochondria and cell death: outer membrane permeabilization and beyond
    Stephen W G Tait
    Department of Immunology, St Jude Childrens Research Hospital, Memphis, Tennessee 38105, USA
    Nat Rev Mol Cell Biol 11:621-32. 2010
    ..MOMP typically leads to cell death irrespective of caspase activity by causing a progressive decline in mitochondrial function, although cells can survive this under certain circumstances, which may have pathophysiological consequences...
  3. ncbi Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis
    H Li
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 94:491-501. 1998
    ..Coexpression of BclxL inhibits all the apoptotic changes induced by tBID. Our results indicate that BID is a mediator of mitochondrial damage induced by Casp8...
  4. ncbi The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta
    Fabio Martinon
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Mol Cell 10:417-26. 2002
    ..of caspase-1 (and caspase-11 in mice), but the mechanism involved in the activation of the proinflammatory caspases remains elusive. Here we report the identification of a caspase-activating complex that we call the inflammasome...
  5. ncbi Non-canonical inflammasome activation targets caspase-11
    Nobuhiko Kayagaki
    Department of Physiological Chemistry, Genentech Inc, South San Francisco, California 94080, USA
    Nature 479:117-21. 2011
    ..These data highlight a unique pro-inflammatory role for caspase-11 in the innate immune response to clinically significant bacterial infections...
  6. ncbi Apoptosis: controlled demolition at the cellular level
    Rebecca C Taylor
    Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland
    Nat Rev Mol Cell Biol 9:231-41. 2008
    ..These proteases target several hundred proteins for restricted proteolysis in a controlled manner that minimizes damage and disruption to neighbouring cells and avoids the release of immunostimulatory molecules...
  7. ncbi The Bcl2 family: regulators of the cellular life-or-death switch
    Suzanne Cory
    The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria 3050, Australia
    Nat Rev Cancer 2:647-56. 2002
    Tissue homeostasis is regulated by apoptosis, the cell-suicide programme that is executed by proteases called caspases. The Bcl2 family of intracellular proteins is the central regulator of caspase activation, and its opposing factions of ..
  8. ncbi Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta
    T Nakagawa
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 403:98-103. 2000
    ..The family of cysteine proteases, the so- called caspases, are critical mediators of programmed cell death, and thus far 14 family members have been identified...
  9. pmc Inhibition of macroautophagy triggers apoptosis
    Patricia Boya
    CNRS UMR 8125, Institut Gustave Roussy, Pavillon de Recherche 1, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    Mol Cell Biol 25:1025-40. 2005
    ..All together, these data indicate that autophagy may be cytoprotective, at least under conditions of nutrient depletion, and point to an important cross talk between type 1 and type 2 cell death pathways...
  10. 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...
  11. ncbi Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade
    P Li
    Howard Hughes Medical Institute, and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA
    Cell 91:479-89. 1997
    ....
  12. ncbi Cellular survival: a play in three Akts
    S R Datta
    Division of Neuroscience, Children s Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115 USA
    Genes Dev 13:2905-27. 1999
  13. ncbi Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis
    R U Jänicke
    Institute of Molecular and Cell Biology, The National University of Singapore, 30 Medical Drive, Singapore 117609, Republic of Singapore
    J Biol Chem 273:9357-60. 1998
    Interleukin 1beta-converting enzyme-like proteases (caspases) are crucial components of cell death pathways...
  14. pmc APP binds DR6 to trigger axon pruning and neuron death via distinct caspases
    Anatoly Nikolaev
    Division of Research, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    Nature 457:981-9. 2009
    ..Our results indicate that APP and DR6 are components of a neuronal self-destruction pathway, and suggest that an extracellular fragment of APP, acting via DR6 and caspase 6, contributes to Alzheimer's disease...
  15. ncbi IAP family proteins--suppressors of apoptosis
    Q L Deveraux
    The Burnham Institute, Program on Apoptosis and Cell Death Research, La Jolla, California 92037 USA
    Genes Dev 13:239-52. 1999
  16. ncbi Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition
    C Du
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA
    Cell 102:33-42. 2000
    ..Overexpression of Smac increases cells' sensitivity to apoptotic stimuli. Smac is the second mitochondrial protein, along with cytochrome c, that promotes apoptosis by activating caspases.
  17. ncbi Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors
    X Luo
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA
    Cell 94:481-90. 1998
    ..The cytochrome c releasing activity of Bid was antagonized by Bcl2. A mutation at the BH3 domain diminished its cytochrome c releasing activity. Bid, therefore, relays an apoptotic signal from the cell surface to mitochondria...
  18. ncbi Apoptotic and non-apoptotic roles of caspases in neuronal physiology and pathophysiology
    Bradley T Hyman
    Neurology Service, Massachusetts General Hospital, 114 16th Street Charlestown, Massachusetts 01029, USA
    Nat Rev Neurosci 13:395-406. 2012
    b>Caspases are cysteine proteases that mediate apoptosis, which is a form of regulated cell death that effectively and efficiently removes extra and unnecessary cells during development...
  19. ncbi An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9
    H Zou
    Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA
    J Biol Chem 274:11549-56. 1999
    ..The stoichiometric ratio of procaspase-9 to APAF-1 is approximately 1 to 1 in the complex. Once activated, caspase-9 disassociates from the complex and becomes available to cleave and activate downstream caspases such as caspase-3.
  20. ncbi IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs
    I Tamm
    The Burnham Institute, La Jolla, California 92037, USA
    Cancer Res 58:5315-20. 1998
    ..induced by overexpression of procaspase-3 and -7 and inhibited the processing of these zymogens into active caspases. In vitro binding experiments indicated that, like other IAP-family proteins, Survivin binds specifically to the ..
  21. ncbi IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer
    Mads Gyrd-Hansen
    Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen DK2200, Denmark
    Nat Rev Cancer 10:561-74. 2010
    ..Recent studies indicate that IAPs not only regulate caspases and apoptosis, but also modulate inflammatory signalling and immunity, mitogenic kinase signalling, proliferation ..
  22. ncbi Mechanisms of caspase activation
    Kelly M Boatright
    Program in Cell Death and Apoptosis Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Curr Opin Cell Biol 15:725-31. 2003
    ..Although this appears to be true for the executioner caspases, recent research points to a distinct activation mechanism for the initiator caspases that trigger the apoptotic ..
  23. pmc Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner
    E A Slee
    Molecular Cell Biology Laboratory, Department of Biology, National University of Ireland, Maynooth, Co Kildare, Ireland
    J Cell Biol 144:281-92. 1999
    ..Here, we report that six additional caspases (caspases-2, -3, -6, -7, -8, and -10) are processed in cell-free extracts in response to cytochrome c, and that ..
  24. ncbi Inhibition of death receptor signals by cellular FLIP
    M Irmler
    Institute of Biochemistry, Lausanne Branch, University of Lausanne, Switzerland
    Nature 388:190-5. 1997
    ..High levels of FLIP(L) protein are also detectable in melanoma cell lines and malignant melanoma tumours. Thus FLIP may be implicated in tissue homeostasis as an important regulator of apoptosis...
  25. ncbi Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor
    Seong Woon Yu
    Department of Neurology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Science 297:259-63. 2002
    ..These data support a model in which PARP-1 activation signals AIF release from mitochondria, resulting in a caspase-independent pathway of programmed cell death...
  26. ncbi BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis
    E H Cheng
    Howard Hughes Medical Institute, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Mol Cell 8:705-11. 2001
    Critical issues in apoptosis include the importance of caspases versus organelle dysfunction, dominance of anti- versus proapoptotic BCL-2 members, and whether commitment occurs upstream or downstream of mitochondria...
  27. ncbi Mammalian caspases: structure, activation, substrates, and functions during apoptosis
    W C Earnshaw
    Institute of Cell and Molecular Biology, University of Edinburgh, Scotland, United Kingdom
    Annu Rev Biochem 68:383-424. 1999
    ..The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases...
  28. ncbi Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked
    J Yang
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Science 275:1129-32. 1997
    ..Overexpression of Bcl-2 prevented the efflux of cytochrome c from the mitochondria and the initiation of apoptosis. Thus, one possible role of Bcl-2 in prevention of apoptosis is to block cytochrome c release from mitochondria...
  29. ncbi Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis
    Shida Yousefi
    Department of Pharmacology, University of Bern, CH 3010 Bern, Switzerland
    Nat Cell Biol 8:1124-32. 2006
    ..Taken together, calpain-mediated Atg5 cleavage provokes apoptotic cell death, therefore, represents a molecular link between autophagy and apoptosis--a finding with potential importance for clinical anticancer therapies...
  30. pmc Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family
    Brendan P Eckelman
    Burnham Institute for Medical Research, La Jolla, California 92037, USA
    EMBO Rep 7:988-94. 2006
    ....
  31. ncbi Apoptosis - the p53 network
    Susan Haupt
    Department of Pharmacy, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel
    J Cell Sci 116:4077-85. 2003
    ..Manipulation of the apoptotic functions of p53 constitutes an attractive target for cancer therapy...
  32. ncbi Caspases in cell survival, proliferation and differentiation
    M Lamkanfi
    Unit of Molecular Signalling and Cell Death, Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology VIB, Ghent University, Ghent Zwijnaarde, Belgium
    Cell Death Differ 14:44-55. 2007
    b>Caspases, a family of evolutionarily, conserved cysteinyl proteases, mediate both apoptosis and inflammation through aspartate-specific cleavage of a wide number of cellular substrates...
  33. ncbi Overview of cell death signaling pathways
    Zhaoyu Jin
    Department of Medicine Hem Onc, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cancer Biol Ther 4:139-63. 2005
    ..b>Caspases are central effectors of apoptosis...
  34. ncbi Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c
    X Liu
    Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Cell 86:147-57. 1996
    ..Cells undergoing apoptosis in vivo showed increased release of cytochrome c to their cytosol, suggesting that mitochondria may function in apoptosis by releasing cytochrome c...
  35. ncbi The Bcl-2 family: roles in cell survival and oncogenesis
    Suzanne Cory
    The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3050, Victoria, Australia
    Oncogene 22:8590-607. 2003
    Apoptosis, the cell-suicide programme executed by caspases, is critical for maintaining tissue homeostasis, and impaired apoptosis is now recognized to be a key step in tumorigenesis...
  36. pmc Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Abeta-induced cell death
    Junichi Hitomi
    Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565 0871, Japan
    J Cell Biol 165:347-56. 2004
    ..Thus, caspase-4 can function as an ER stress-specific caspase in humans, and may be involved in pathogenesis of Alzheimer's disease...
  37. ncbi Identification of paracaspases and metacaspases: two ancient families of caspase-like proteins, one of which plays a key role in MALT lymphoma
    A G Uren
    Genentech Inc, South San Francisco, California 94080, USA
    Mol Cell 6:961-7. 2000
    b>Caspases are cysteine proteases essential to apoptosis. We have identified two families of caspase-like proteins, Paracaspases (found in metazoans and Dictyostelium) and metacaspases (found in plants, fungi, and protozoa)...
  38. ncbi Cell death independent of caspases: a review
    Linda E Bröker
    Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
    Clin Cancer Res 11:3155-62. 2005
    Patterns of cell death have been divided into apoptosis, which is actively executed by specific proteases, the caspases, and accidental necrosis...
  39. ncbi Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway
    C Tournier
    Howard Hughes Medical Institute, Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Science 288:870-4. 2000
    ..These data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway...
  40. ncbi Caspase family proteases and apoptosis
    Ting Jun Fan
    College of Marine Life Sciences, Division of Life Science and Technology, Ocean University of China, Qingdao 266003, China
    Acta Biochim Biophys Sin (Shanghai) 37:719-27. 2005
    ..b>Caspases, closely associated with apoptosis, are aspartate-specific cysteine proteases and members of the interleukin-..
  41. ncbi Arabidopsis type I metacaspases control cell death
    Nuria S Coll
    Department of Biology, 108 Coker Hall, University of North Carolina UNC, CB 3280, Chapel Hill, NC 27599 3280, USA
    Science 330:1393-7. 2010
    Metacaspases are distant relatives of animal caspases found in protozoa, fungi, and plants. Limited experimental data exist defining their function(s), despite their discovery by homology modeling a decade ago...
  42. ncbi Cellular FLICE-inhibitory protein splice variants inhibit different steps of caspase-8 activation at the CD95 death-inducing signaling complex
    A Krueger
    Tumor Immunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
    J Biol Chem 276:20633-40. 2001
    ..Our results indicate that c-FLIP(L) induces a conformation of procaspase-8 that allows partial but not complete proteolytical processing, whereas in contrast c-FLIP(S) even prevents partial procaspase-8 activation at the DISC...
  43. ncbi Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3
    H Zou
    Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75235, USA
    Cell 90:405-13. 1997
    ..The COOH-terminal region of Apaf-1 comprises multiple WD repeats, which are proposed to mediate protein-protein interactions. Cytochrome c binds to Apaf-1, an event that may trigger the activation of caspase-3, leading to apoptosis...
  44. 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...
  45. pmc An AIF orthologue regulates apoptosis in yeast
    Silke Wissing
    Institute for Physiological Chemistry, University of Tubingen, Hoppe Seyler Strasse 4, Tuebingen 72076, Germany
    J Cell Biol 166:969-74. 2004
    ..We conclude that Ynr074cp is a cell death effector in yeast and rename it AIF-1 (Aif1p, gene AIF1)...
  46. pmc Quantitative analysis of pathways controlling extrinsic apoptosis in single cells
    John G Albeck
    Department of Systems Biology, Harvard Medical School, WAB Room 438, 200 Longwood Avenue, Boston, MA 02115, USA
    Mol Cell 30:11-25. 2008
    Apoptosis in response to TRAIL or TNF requires the activation of initiator caspases, which then activate the effector caspases that dismantle cells and cause death...
  47. pmc XIAP discriminates between type I and type II FAS-induced apoptosis
    Philipp J Jost
    The Walter and Eliza Hall Institute of Medical Research, Melbourne University, Parkville, Victoria 3050, Australia
    Nature 460:1035-9. 2009
    ..In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including ..
  48. ncbi PUMA, a novel proapoptotic gene, is induced by p53
    K Nakano
    Regulation of Cell Growth Laboratory, National Cancer Institute at Frederick, Maryland 21702, USA
    Mol Cell 7:683-94. 2001
    ..Antisense inhibition of PUMA expression reduced the apoptotic response to p53, and PUMA is likely to play a role in mediating p53-induced cell death through the cytochrome c/Apaf-1-dependent pathway...
  49. ncbi Executioner caspase-3, -6, and -7 perform distinct, non-redundant roles during the demolition phase of apoptosis
    E A Slee
    Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland
    J Biol Chem 276:7320-6. 2001
    Apoptosis is orchestrated by a family of cysteine proteases known as the caspases. Fourteen mammalian caspases have been identified, three of which (caspase-3, -6, and -7) are thought to coordinate the execution phase of apoptosis by ..
  50. 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...
  51. ncbi An antagonist decoy receptor and a death domain-containing receptor for TRAIL
    G Pan
    Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
    Science 277:815-8. 1997
    ..Another death domain-containing receptor for TRAIL (designated as death receptor-5), which preferentially engaged a FLICE (caspase-8)-related death protease, was also identified...
  52. ncbi Apoptosis and melanoma chemoresistance
    Maria S Soengas
    Department of Dermatology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 28109, USA
    Oncogene 22:3138-51. 2003
    ..With this knowledge in hand, the challenge is now to devise strategies potent enough to compensate or bypass these cell death defects and improve the actual poor prognosis of patients at late stages of the disease...
  53. ncbi Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Crit Care Med 27:1230-51. 1999
    ..The purpose of this study was to determine whether apoptosis is a major mechanism of cell death in patients with sepsis. The activities of caspase-3 and the antiapoptotic protein, BCL-2, were investigated also...
  54. ncbi The inhibitors of apoptosis (IAPs) and their emerging role in cancer
    E C LaCasse
    Apoptogen Inc, CHEO Research Institute, Ottawa, Ontario, Canada
    Oncogene 17:3247-59. 1998
    ..Overall a picture consistent with an IAP role in tumour progression rather than tumour initiation is emerging making the IAPs an attractive therapeutic target...
  55. ncbi Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139
    E P Rogakou
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 275:9390-5. 2000
    ..These results indicate that gamma-H2AX formation is an early chromatin modification following initiation of DNA fragmentation during apoptosis...
  56. ncbi Expansion and evolution of cell death programmes
    Alexei Degterev
    Tufts University, School of Medicine, Department of Biochemistry, 136 Harrison Ave, Boston, Massachusetts 02111, USA
    Nat Rev Mol Cell Biol 9:378-90. 2008
    ..Here we examine how and why these different cell death programmes have evolved, with an eye towards new cytoprotective therapeutic opportunities...
  57. ncbi Apoptosis and necrosis: detection, discrimination and phagocytosis
    Dmitri V Krysko
    Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, 9052 Ghent, Belgium
    Methods 44:205-21. 2008
    ..cleavage and cytochrome c release by western blotting); (4) release of extracellular markers in the supernatant (caspases, HMGB-1 and cytokeratin 18)...
  58. ncbi Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule
    N Holler
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Nat Immunol 1:489-95. 2000
    ..We show here that Fas kills activated primary T cells efficiently in the absence of active caspases, which results in necrotic morphological changes and late mitochondrial damage but no cytochrome c release...
  59. pmc Mathematical modeling identifies inhibitors of apoptosis as mediators of positive feedback and bistability
    Stefan Legewie
    Institute for Theoretical Biology, Humboldt University, Berlin, Germany
    PLoS Comput Biol 2:e120. 2006
    ..g., Casp3 and Casp9), the feedback mechanism described in this paper is likely to be a widespread principle on how cells achieve ultrasensitivity, bistability, and irreversibility...
  60. ncbi BCL-2 family members and the mitochondria in apoptosis
    A Gross
    Department of Pathology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 13:1899-911. 1999
  61. ncbi Regulation of caspases in the nervous system implications for functions in health and disease
    Carol M Troy
    Department of Pathology and Cell Biology, Taub Center for the Study of Alzheimer s Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, USA
    Prog Mol Biol Transl Sci 99:265-305. 2011
    b>Caspases, initially identified as a family of proteases regulating cell death, have been found to have nonapoptotic functions as well. Some family members are critical for mediating programmed cell death in development...
  62. ncbi A caspase-related protease regulates apoptosis in yeast
    Frank Madeo
    Institute for Physiological Chemistry, University of Tubingen, Hoppe Seyler Strasse 4, 72076 Tubingen, Germany
    Mol Cell 9:911-7. 2002
    ..Here we investigate Yor197w, a yeast protein with structural homology to mammalian caspases, and demonstrate caspase-like processing of the protein...
  63. ncbi Apoptotic pathways: ten minutes to dead
    Douglas R Green
    La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
    Cell 121:671-4. 2005
    ..The emerging, if preliminary, perspective these new studies provide may represent either a refinement of our views of how cells die or, perhaps, the beginnings of what amounts to a reformulation of our ideas...
  64. ncbi Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I
    M L Coleman
    CRC Centre for Cell and Molecular Biology, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
    Nat Cell Biol 3:339-45. 2001
    ..The activity of ROCK proteins is both necessary and sufficient for formation of membrane blebs and for re-localization of fragmented DNA into blebs and apoptotic bodies...
  65. ncbi Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP)
    Han C Dan
    Departments of Pathology and Interdisciplinary Oncology, University of South Florida College of Medicine and H Lee Moffitt Cancer Center, Tampa, Florida 33612, USA
    J Biol Chem 279:5405-12. 2004
    ..These data identify XIAP as a new downstream target of Akt and a potentially important mediator of the effect of Akt on cell survival...
  66. ncbi Coupling endoplasmic reticulum stress to the cell death program
    R V Rao
    Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA
    Cell Death Differ 11:372-80. 2004
    ....
  67. ncbi Caspases in apoptosis and beyond
    J Li
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Oncogene 27:6194-206. 2008
    ..During the past 15 years, a plethora of knowledge has been obtained on the mammalian caspases, the homologs of CED-3, with regard to their distinct physiological functions, their substrates, different ..
  68. pmc Human caspases: activation, specificity, and regulation
    Cristina Pop
    Program in Apoptosis and Cell Death Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Biol Chem 284:21777-81. 2009
    b>Caspases are intracellular proteases that propagate programmed cell death, proliferation, and inflammation. Activation of caspases occurs by a conserved mechanism subject to strict cellular regulation...
  69. ncbi Role of Bcl-2 family proteins and caspases in the regulation of apoptosis
    Mohammad Shamsul Ola
    Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, KSA
    Mol Cell Biochem 351:41-58. 2011
    ..of downstream cascade of events, releasing of various apoptotic mediators from mitochondria and activation of caspases, important for the cell fate...
  70. ncbi Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8
    Li Yu
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Science 304:1500-2. 2004
    b>Caspases play a central role in apoptosis, a well-studied pathway of programmed cell death...
  71. ncbi Morphologic and biochemical hallmarks of apoptosis
    A Saraste
    Department of Anatomy, University of Turku, Finland
    Cardiovasc Res 45:528-37. 2000
    ..Activation of cysteine proteases called caspases plays a major role in the execution of apoptosis...
  72. ncbi A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD
    M Enari
    Department of Genetics, Osaka University Medical School, Suita, Japan
    Nature 391:43-50. 1998
    ..to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity; caspases activated by apoptotic stimuli then cleave ICAD, allowing CAD to enter the nucleus and degrade chromosomal DNA.
  73. ncbi Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4
    Shiqian Qi
    Ministry of Education Protein Science Laboratory, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China
    Cell 141:446-57. 2010
    ..The structure of the CED-4 apoptosome reveals shared principles for the NB-ARC family of AAA(+) ATPases and suggests a mechanism for the activation of CED-3...
  74. ncbi Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death
    N Joza
    Amgen Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2C1
    Nature 410:549-54. 2001
    ..Our data provide genetic evidence for a caspase-independent pathway of programmed cell death that controls early morphogenesis...
  75. ncbi Classification of the caspase-hemoglobinase fold: detection of new families and implications for the origin of the eukaryotic separins
    L Aravind
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA
    Proteins 46:355-67. 2002
    ..The acquisition of the caspase-hemoglobinase-fold domains by eukaryotes might have been critical in the evolution of important eukaryotic processes, such as mitosis and programmed cell death...
  76. ncbi Cytochrome c: functions beyond respiration
    Yong Ling P Ow
    The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Ontario M5G 2C1, Canada
    Nat Rev Mol Cell Biol 9:532-42. 2008
    ..As well as its role in canonical intrinsic apoptosis, cytochrome c amplifies signals that are generated by other apoptotic pathways and participates in certain non-apoptotic functions...
  77. ncbi An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12
    Nobuhiro Morishima
    Bioarchitect Research Group, RIKEN The Institute of Physical and Chemical Research, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    J Biol Chem 277:34287-94. 2002
    ..To examine the role of caspase-12 in the activation of downstream caspases, we used a caspase-12-binding protein, which we identified in a yeast two-hybrid screen, for regulation of ..
  78. ncbi Inflammatory caspases and inflammasomes: master switches of inflammation
    F Martinon
    Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Epalinges, Switzerland
    Cell Death Differ 14:10-22. 2007
    ..enzyme (ICE/caspase-1), the first identified member of a family of proteases currently known as caspases. Caspase-1 is the prototypical member of a subclass of caspases involved in cytokine maturation termed ..
  79. ncbi Caspase substrates and cellular remodeling
    Emily D Crawford
    Department of Pharmaceutical Chemistry and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158 2330, USA
    Annu Rev Biochem 80:1055-87. 2011
    The caspases are unique proteases that mediate the major morphological changes of apoptosis and various other cellular remodeling processes...
  80. pmc Metacaspases
    L Tsiatsiani
    Department of Plant Systems Biology, VIB, Ghent, Belgium
    Cell Death Differ 18:1279-88. 2011
    ..are cysteine-dependent proteases found in protozoa, fungi and plants and are distantly related to metazoan caspases. Although metacaspases share structural properties with those of caspases, they lack Asp specificity and cleave ..
  81. ncbi The Fas signaling pathway: more than a paradigm
    Harald Wajant
    Institute of Cell Biology and Immunology, Allmandring 31, University of Stuttgart, 70 569 Stuttgart, Germany
    Science 296:1635-6. 2002
    ....
  82. ncbi Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis
    S Kothakota
    Chiron Corporation, Emeryville, CA 94608, USA
    Science 278:294-8. 1997
    ..Thus, cleaved gelsolin may be one physiological effector of morphologic change during apoptosis...
  83. ncbi Endonuclease G regulates budding yeast life and death
    Sabrina Buttner
    Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria
    Mol Cell 25:233-46. 2007
    ..Deletion of NUC1 diminishes apoptotic death when mitochondrial respiration is increased but enhances necrotic death when oxidative phosphorylation is repressed, pointing to dual--lethal and vital--roles for EndoG...
  84. pmc Caspases and kinases in a death grip
    Manabu Kurokawa
    Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA
    Cell 138:838-54. 2009
    The complex process of apoptosis is orchestrated by caspases, a family of cysteine proteases with unique substrate specificities...
  85. ncbi Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes
    Olivier Micheau
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Cell 114:181-90. 2003
    ..Thus, TNFR1-mediated-signal transduction includes a checkpoint, resulting in cell death (via complex II) in instances where the initial signal (via complex I, NF-kappa B) fails to be activated...
  86. ncbi Caspase activation by anticancer drugs: the caspase storm
    Zhimin Tao
    Department of Chemistry, Syracuse University, 1 014 CST, Syracuse, New York 13244, USA
    Mol Pharm 4:583-95. 2007
    ..that this substrate rapidly enters cells where it is efficiently cleaved at the aspartate residue by specific caspases, yielding the fluorescent compound 7-amino-4-trifluoromethyl coumarin (AFC)...
  87. pmc Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis
    Sabrina L Spencer
    Center for Cell Decision Processes, Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 459:428-32. 2009
    ..Our results have implications for understanding 'fractional killing' of tumour cells after exposure to chemotherapy, and for variability in mammalian signal transduction in general...
  88. ncbi Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53
    Jianze Li
    Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089 9176, USA
    J Biol Chem 281:7260-70. 2006
    ..mediated by Apaf-1 is an integral part of ER stress-induced apoptosis and that ER stress activates different caspases through Apaf-1-dependent and -independent mechanisms...
  89. ncbi The mitochondrial death pathway and cardiac myocyte apoptosis
    Michael T Crow
    Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Rm 5A 58, Baltimore, MD 21224, USA
    Circ Res 95:957-70. 2004
    ..Each of these pathways has been implicated in myocardial pathology. In this review, we summarize recent advances in the understanding of the intrinsic pathway and how it relates to cardiac myocyte death and heart disease...
  90. pmc Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis
    Y Lin
    Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Genes Dev 13:2514-26. 1999
    ..Further more, RIP cleavage was also detected in other death receptor-mediated apoptosis. Therefore, our study provides a potential mechanism to convert cells from life to death in death receptor-mediated apoptosis...
  91. ncbi Caspase function in programmed cell death
    S Kumar
    Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, SA, Australia
    Cell Death Differ 14:32-43. 2007
    ..Following the discovery of CED-3, caspases have been cloned from several vertebrate and invertebrate species...
  92. pmc Caspases and cancer
    M Olsson
    Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
    Cell Death Differ 18:1441-9. 2011
    ..This cell death modality is executed by caspases and several upstream regulatory factors, which direct their proteolytic activity, have been defined as either ..
  93. ncbi On the role of Hsp27 in regulating apoptosis
    C G Concannon
    Department of Biochemistry and National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
    Apoptosis 8:61-70. 2003
    ..This article will review recent advances in the field and will address some of the potential mechanisms by which Hsp27 functions as an anti-apoptotic molecule...
  94. pmc Autophagy, not apoptosis, is essential for midgut cell death in Drosophila
    Donna Denton
    Department of Haematology, Centre for Cancer Biology, Adelaide, SA, Australia
    Curr Biol 19:1741-6. 2009
    Most developmentally programmed cell death in metazoans is mediated by caspases. During Drosophila metamorphosis, obsolete tissues, including the midgut and salivary glands, are removed by programmed cell death [1]...
  95. ncbi Human ICE/CED-3 protease nomenclature
    E S Alnemri
    Cell 87:171. 1996
  96. ncbi Cleavage of Mcl-1 by caspases impaired its ability to counteract Bim-induced apoptosis
    Magali Herrant
    INSERM U526, Physiopathologie de la Survie et de la Mort Cellulaires et Infections Virales, Equipe Labellisée par la Ligue Nationale Contre le Cancer, IFR50, Faculte de Medecine, Avenue de Valombrose, 06107 Nice Cedex 2, France
    Oncogene 23:7863-73. 2004
    ..We report here that Mcl-1 is a new substrate for caspases during induction of apoptosis...
  97. ncbi Induction of autophagic cell death in malignant glioma cells by arsenic trioxide
    Takao Kanzawa
    Department of Neurosurgery, Mount Sinai School of Medicine, New York, New York 10029, USA
    Cancer Res 63:2103-8. 2003
    ..These findings suggest that As(2)O(3) at a clinically safe concentration may be an effective chemotherapeutic agent for malignant gliomas...
  98. pmc Mathematical modeling reveals threshold mechanism in CD95-induced apoptosis
    M Bentele
    Division Theoretical Bioinformatics, German Caner Research Center DKFZ, Heidelberg 69120, Germany
    J Cell Biol 166:839-51. 2004
    ..Our model describes the regulation of apoptosis on a systems level and resolves the important question of a threshold mechanism for the regulation of apoptosis...
  99. ncbi On the origin, evolution, and nature of programmed cell death: a timeline of four billion years
    J C Ameisen
    EMI U 9922 INSERM Université Paris 7, IFR 02, Hopital Bichat Claude Bernard, AP HP, 46 rue Henri Huchard, 75877 Paris Cedex 18, France
    Cell Death Differ 9:367-93. 2002
    ..And a new view of the regulated cell suicide pathways emerges when one attempts to ask the question of when and how they may have become selected during evolution, at the level of ancestral single-celled organisms...
  100. pmc Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes
    M Woo
    Amgen Institute Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario M5G2C1, Canada
    Genes Dev 12:806-19. 1998
    b>Caspases are fundamental components of the mammalian apoptotic machinery, but the precise contribution of individual caspases is controversial. CPP32 (caspase 3) is a prototypical caspase that becomes activated during apoptosis...
  101. pmc Malt1-dependent RelB cleavage promotes canonical NF-kappaB activation in lymphocytes and lymphoma cell lines
    Stephan Hailfinger
    Department of Biochemistry, University of Lausanne, CH 1066 Epalinges, Switzerland
    Proc Natl Acad Sci U S A 108:14596-601. 2011
    ..These findings identify a central role for Malt1-dependent RelB cleavage in canonical NF-κB activation and thereby provide a rationale for the targeting of Malt1 in immunomodulation and cancer treatment...

Research Grants73

  1. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..
  2. Targeting Inflammation for the Amelioration of Cisplatin-Hearing Loss
    Vickram Ramkumar; Fiscal Year: 2011
    ..However, inhibition of caspases, p53, or activation of DNA repair enzymes may promote the development of tumors or promote tumor chemoresistance...
  3. Therapeutic Effect of a Novel Antioxidant on Degenerative Eye Disorders
    Nuran Ercal; Fiscal Year: 2012
    ..of antioxidant enzymes, and the expression of pro-apoptotic and apoptotic proteins such as cytochrome c and caspases. We will also study protein oxidation of crystallins, lipid peroxidation, and protein bound GSH and cysteine...
  4. A fully validated assay to identify activators of ERSR in human glioma cells: ide
    Maurizio Grimaldi; Fiscal Year: 2012
    ..Spiperone does indeed activate ERSR, upregulate native GRP78, activate ER-associated caspases and cause marked death of glioma cells...
  5. Prevention of Retinal Degeneration by Crystallins in Experimental Uveitis
    Narsing A Rao; Fiscal Year: 2011
    ..upregulated 1A crystallin interacts with the oxidative stress-induced nitrated cyto c, blocking the activation of caspases, and preventing apoptosis of photoreceptors...
  6. Apoptosis and Trophoblast Fusion
    NEAL STEWART ROTE; Fiscal Year: 2010
    ..Our preliminary data suggest that several apoptosis-related proteins, particularly caspases 3, 8, and 14, may be critical participants in trophoblast differentiation...
  7. Visualization of ototoxic mitochondrial dysfunction in mammalian hair cells
    Shelley A Batts; Fiscal Year: 2012
    ..from the space between the mitocondrion's inner and outer membrane, which once in the cytosol, activate caspases that destroy the cell...
  8. Role of The Jak-Stat Pathway in Ischemic Preconditioning
    Yu Ting Xuan; Fiscal Year: 2010
    ..by examining their effects on the release of cytochrome c and Smac from mitochondria, on the activation of caspases (caspase-3, 8, and 9) and the cleavage of PARP, and on the expression of pro- and anti-apoptotic proteins...
  9. Investigation of underlying mechanisms of sex differences in cerebral ischemia
    Chad S Siegel; Fiscal Year: 2010
    ..We will investigate the role of caspase-mediated cell death proteins (XIAP, Apaf-1, Smac/DIABLO, caspases, and cyt-c) in both male and female mice after experimental stroke...
  10. Effect of constitutive Type 2 NF-kB on adipogenesis
    LOTUS KYI LOO; Fiscal Year: 2010
    ..of clAPs has been a major goal in advancing cancer therapeutics, as clAPs are believed to antagonize activated caspases and are often amplified in human cancers...
  11. Toll-Like Receptor-Mediated Photoreceptor Mitochondrial DNA Damage
    Narsing A Rao; Fiscal Year: 2010
    ..4. Localize oxidative stress-mediated mitochondrial DNA damage and caspases in the retina with upregulation of TLRs and demonstrate augmentation of retinal damage with T-cell-mediated ..
  12. Heat Shock-Induced Apoptosis
    Shawn B Bratton; Fiscal Year: 2012
    ..We have recently shown that heat shock does not require any of the known initiator caspases or their activating complexes to induce apoptosis...
  13. Histone Deacetylation Regulates Growth Plate Development
    Lei Wei; Fiscal Year: 2013
    ..Specific Aim 2: To determine whether: 2a) caspases degrade HDAC4;2b) p38 MAPK regulates expression or activity of capsases 2 and 3;2c) Runx2 expression is dependent ..
  14. Investigating the mechanism of TNFalpha mediated cell death in oligodendrocytes
    Junying Yuan; Fiscal Year: 2013
    ..However, for most cell types analyzed so far, necroptosis is only activated when the activation of caspases is inhibited by chemical inhibitors or by genetic mutation...
  15. Inflammatory Proteases, Ubiquitin Proteasome System, and Myocyte Death
    Abdelkarim Sabri; Fiscal Year: 2012
    ..Aim 3 will identify the signaling pathways downstream from FAK that lead to the activation of initiator caspases during CG-induced myocyte anoikis...
  16. C/EBP beta SIGNALS HEPATOCYTE PROLIFERATION AND SURVIVAL
    Mario Chojkier; Fiscal Year: 2012
    ..a novel non- transcriptional role of C/EBPI3PThr z_7as the first mammalian protein acting as an inhibitor of caspases. As expected, we have found that the nonphosphorylatable C/EBP_ Ala217mutant prevents hepatocyte proliferation ..
  17. Keratin Biology and Disease Aspects in Simple Epithelia
    Bishr Omary; Fiscal Year: 2013
    ..aspects of keratin regulation;namely glycosylation, keratin associated proteins (KAPs), and keratin cleavage by caspases, and (b) an unbiased approach to explore results from expression profiling analysis of wild-type and keratin-8 ..
  18. Regulation of caspase-1 by Sod2 in the heart
    Kumuda C Das; Fiscal Year: 2010
    b>Caspases are a family of cysteine proteases that include at least 14 members, and play a critical role in mammalian apoptosis or proteolytic activation of cytokines...
  19. Establishing a neuroprotection model in the nonhuman primate to support translati
    MATTHEW SWAN LAWRENCE; Fiscal Year: 2013
    ..inhibitor Nec-1 and IDN-6556, both of which have been demonstrated to be potent inhibitors of RIP kinase 1 and caspases, respectively, and to be well tolerated and bioavailable following IVT injection, with combined clinical ..
  20. INFLAMMATORY RESPONSES IN THE TOXICITY OF RICIN
    Bruce Magun; Fiscal Year: 2009
    ..Simultaneously, ricin activates apoptotic pathways, via engagement of apical caspases 8 and 9, which lead to cell death...
  21. Immunopathogenesis in Histoplasmosis
    George S Deepe; Fiscal Year: 2012
    ..Inhibiting the activation of caspases, which are proteases involved in the apoptotic cascade, exacerbates infection...
  22. CONTROL OF APOPTOSIS BY DROSOPHILA CELL DEATH GENES
    Hermann Steller; Fiscal Year: 2012
    ..A central step in the execution of apoptosis is the activation of a specific class of cysteine proteases, termed caspases that are widely expressed as inactive zymogens...
  23. Antioxidants and Antiinflammatory in Colorectal Cancer
    Ah Ng Tony Kong; Fiscal Year: 2012
    ..biomarkers;(3) ITCs induce apoptotic cell death via mitochondria cytochrome c release and activation of caspases in HT-29 colon cancer cells;(4) ITCs activate MAPKs leading to cell cycle arrest in HT-29 cells...
  24. Proteomics of Cell Death via 2-D Microfluidic Profiling
    DON DEVOE; Fiscal Year: 2009
    ..A family of cysteine proteases, called Caspases, are conserved throughout animals and function to dismantle cells during programmed cell death by proteolysis...
  25. Forms of HCV NS5A in vivo
    Craig E Cameron; Fiscal Year: 2013
    ..The additional forms of NS5A detected in liver tissue are remarkably similar to those observed in cell lines when caspases are activated and the abundance of the PKA- phosphorylated species correlates well with the amount of liver ..
  26. Mechanisms and Modulation of Cell Death in Traumatic Brain Injury
    ALAN IRA FADEN; Fiscal Year: 2012
    ..injury (TBI), or traumatic neuronal injury in vitro, causes neuronal apoptosis, in part through activation of caspases. Inhibition of caspase-3, in both in vivo or in vitro trauma models, reduces post-traumatic apoptosis, and ..
  27. Astrovirus structure and replication
    Yizhi Jane Tao; Fiscal Year: 2013
    ..viral capsid by host extracellulr proteases;(2) The 125aa C-terminal domain of the viral CP is removed by host caspases following viral assembly;and (3) Astroviruses appear to encode a VPg similar to the VPg found in caliciviruses, ..
  28. NLR Family Proteins: Mechanisms and Regulation
    John C Reed; Fiscal Year: 2012
    ..for recruiting signaling proteins brought to the complex via PYD, CARD, or other domains, including inflammatory Caspases involved in cytokine processing and apoptosis. These proteins complexes have been dubbed, "inflammasomes"...
  29. Molecular mechanisms of chemoresistance in breast cancer
    Manabu Kurokawa; Fiscal Year: 2013
    ..which promotes nucleation of a structure known as the apoptosome to activate cysteine proteases called caspases. In contrast to untransformed cells, cancer cells exhibit marked resistance to apoptosis by blocking ..
  30. Systematic analysis of cell death regulation in mosquitoes
    Lei Zhou; Fiscal Year: 2009
    ..They bind to caspases and inhibit the activity of these [unreadable]deadly[unreadable] enzymes...
  31. CYTOTOXIC LYMPHOCYTES AND HSV-1 CORNEAL LESIONS
    Robert L Hendricks; Fiscal Year: 2013
    ..also test the hypothesis that the HSV-1 regulatory protein ICP4, via predicted GrB cleavage sites, competes with caspases as GrB substrate and is inactivated by cleavage resulting in GrB inhibition of HSV-1 reactivation without ..
  32. Programmed necrosis in Immune Responses
    Francis Ka Ming Chan; Fiscal Year: 2013
    ..Mechanistically, programmed necrosis is optimally induced when caspases are inhibited, such as that during infections with viruses that encode caspase inhibitors...
  33. TARGETS OF AMINO ACID RESTRICTION IN PROSTATE CANCER
    Gary G Meadows; Fiscal Year: 2009
    ..pathway and the Akt pathway leading to loss of mitochondrial integrity with consequent activation of effector caspases. The specific aims are: 1) Identify if FAK/Cas/Crk or Rho/Ras pathway is the molecular target(s) of specific ..
  34. Unfolded Protein Response in Lens Epithelial Cells
    Toshimichi Shinohara; Fiscal Year: 2012
    ..The UPR death pathway activates specific proteins including caspases, stimulates Ca++ release and the over production of reactive oxygen species (ROS), and results in LEC death...
  35. CARP-1: A Potential Therapeutic Agent for Breast Cancer
    ARUN KUMAR RISHI; Fiscal Year: 2013
    ..CARP-1, leads to increased CARP- 1 levels, activates pro-apoptotic p38 mitogen-activated protein kinase (MAPK), caspases-9 and 3, and apoptosis...
  36. Pyruvate: Powerful Brain Protection after Cardiac Arrest
    Robert T Mallet; Fiscal Year: 2013
    ..mRNA and protein content, signaling kinase activation, neutrophil infiltration, and activities of proapoptotic caspases, pro-inflammatory matrix metalloproteinases, and the cytoprotective enzyme endothelial nitric oxide synthase will ..
  37. Progranulin, TDP-43 and Cell Death
    Leonard Petrucelli; Fiscal Year: 2013
    ..that decreasing PGRN expression activates cell death pathways leading to pathological processing of TDP-43 by caspases in cell culture models...
  38. IL-1 beta Signaling in Diabetic Retinopathy
    Susanne Mohr; Fiscal Year: 2010
    ..b>Caspases are a family of proteolytic enzymes, and participate in one of the two distinct signaling pathways: (1) ..
  39. Mechanisms of Hypothermic Protection from Ischemia/Reperfusion Cardiac Injury
    Kimm J Hamann; Fiscal Year: 2010
    ..provides protection and prevents release of pro-apoptotic mitochondrial proteins cyt c and activation of caspases. We hypothesize that activation of p53 during I/R leads to activation of Bax and/or Bak and hypothermic blockade ..
  40. How can caspases control intracellular pulmonary pathogens
    Amal O Amer; Fiscal Year: 2010
    ..However, the role of other caspases in Legionella infection is still unknown...
  41. Molecular Characterization of Neural Stem Cell Apoptosis
    KEVIN AARON ROTH; Fiscal Year: 2012
    ..specific and are dependent on interactions between an array of molecules including p53, Bcl-2 family members, caspases, and a variety of autophagy-associated proteins...
  42. Molecular Mechanism of Mule in DNA Damage Response and Tumorigenesis
    Qing Zhong; Fiscal Year: 2013
    ..Once this cell death pathway is triggered, cytotoxic factors are released from mitochondria to activate caspases that induce apoptosis...
  43. Na-K-Cl cotransporter in Glioblastoma Multiforme
    Dandan Sun; Fiscal Year: 2013
    ..The reduction of intracellular ionic strength has been suggested to play a permissive role in activation of caspases and triggering the entire caspase cascade and apoptotic machinery...
  44. XIAP Gene Therapy in Huntington's Disease
    Michael G Kaplitt; Fiscal Year: 2013
    ..inhibitor proteins, which is known to bind to and block the function of effectors of apoptosis including caspases and mitochondrial cell death proteins Smac and Omi...
  45. Autophagy and control of photoreceptor apoptosis
    David N Zacks; Fiscal Year: 2013
    ..Activation of the FAS-receptor leads to downstream activation of serine proteases (caspases) that ultimately result in the death and removal of the photoreceptor from the retina...
  46. RIPK-dependent necrosis in development and cancer
    Douglas R Green; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): While the role of caspases in apoptosis is well established, little is known about the role of these proteases in the process of programmed necrosis...
  47. Protection against sarin-induced neurotoxicity via an in vivo caspase inhibitor
    David R Cool; Fiscal Year: 2011
    ..Confocal microscopy and immunostaining will be used to analyze tissue sections for specific caspases and other biomarkers of cell death...
  48. HOW ENVIRONMENTAL CHEMICALS IMPAIR IMMUNITY
    David Sherr; Fiscal Year: 2009
    ..Specifically, we will: a) determine the roles of caspases-2 and -8 in mitochondrial activation mediated by Bid, b) assess the contribution of JNK, PKR and p53 in caspase-..
  49. NEUROTROPHIC FACTOR DEPRIVATION AND NEURONAL CELL DEATH
    Lloyd A Greene; Fiscal Year: 2013
    ..Induction of Bim promotes release of mitochondrial proteins and activation of caspases, resulting in neuron death...
  50. Structural Analysis of the GPI Transamidase Complex
    Anant K Menon; Fiscal Year: 2012
    ..The catalytic subunit, Gpi8, shares homology with caspases;the functional role of the other subunits is unclear, but all are required for GPIT activity...
  51. Necroptosis and Neuroprotection in AMD
    Demetrios Vavvas; Fiscal Year: 2013
    ..We propose to study whether the RIP kinase pathway in combination with caspases can be a novel therapeutic target in other animal models of retinal degeneration such as AMD...
  52. Overcoming therapeutic resistance of gliomas
    Khalid A Shah; Fiscal Year: 2013
    ..our preliminary studies on the downregulation of ERK, activation of JNK and p38 and subsequent up- regulation of caspases in oHSV and TRAIL resistant glioma cells treated with oHSV-TRAIL, we hypothesize that oHSV will target cell ..
  53. Hepatocellular Carcinoma in Antitrypsin Deficiency
    David H Perlmutter; Fiscal Year: 2012
    ..of ATZ in the ER activates a distinct profile of signaling pathways including NFKB, ER- and mitochondrial-caspases and autophagy but not the unfolded protein response...
  54. Topoisomerase ll Beta in Myeloid Differentiation by Retionids
    RAM N GANAPATHI; Fiscal Year: 2010
    ..For these studies we will examine activation of TRAIL, caspases (9, 8 and 3) and PARP, cleavage of BID and release of cytochrome c in ATRA treated topo IIbeta -deficient AML ..
  55. Role of apoptosis for regenerative proliferation
    Andreas Bergmann; Fiscal Year: 2013
    ..suggests that regenerative AiP of amputated or otherwise damaged tissues including tumors depends on apoptotic caspases (highly specific cell death proteases) in a non-apoptotic function...
  56. FADD Signaling in Cancer Cells
    Andrew M Thorburn; Fiscal Year: 2013
    ..The molecular mechanisms by which FADD activates caspases upon TRAIL receptor stimulation are quite well understood, however mechanisms of TRAIL resistance are still ..
  57. PP2A B-beta a novel apoptosis regulator
    José Carlos Crispín; Fiscal Year: 2013
    ..Activation of caspases and Bcl-2-related proteins along with mitochondrial integrity will be evaluated...
  58. Caspase-6 allosteric inhibitors: activity probes and neurodegeneration treatment
    JEANNE ANN HARDY; Fiscal Year: 2013
    ..probes exist because all available probes for use in cell or animal models function at the active sites of caspases and all caspases have very similar active sites...
  59. Posttranslational processing of tau: function & dysfunc.
    Gail Johnson; Fiscal Year: 2009
    ..targeting, that these interactions are regulated by site-specific tau phosphorylation and that tau cleaved by caspases accumulates because it is no longer an efficient substrate of the proteasome system...
  60. Huntington's Disease: Analysis of Proteolysis
    ROBERT NORMAN O'BRIEN; Fiscal Year: 2013
    ..of mutant HTT protein is caused by production of protein fragments by several protease families including caspases, calpains and matrix metalloproteinases (protein degrading enzymes)...
  61. Mechanistic targets for intervention in sepsis-induced renal injury
    Philip R Mayeux; Fiscal Year: 2012
    ..Our preliminary data show that inhibition of inducible nitric oxide synthase, inhibition of caspases, or inhibition of p53 each can prevent CLP-induced renal failure in mice...
  62. Inhibition of Cytochrome c-induced Caspase Activation
    SALLY A KORNBLUTH; Fiscal Year: 2013
    ..Active caspase 9 then activates the executioner caspases 3 and 7 to dismantle the doomed cell...
  63. A HTS Assay for Identifying Anti-Viral Drugs Against Arbovirus Infections
    Qianjun Li; Fiscal Year: 2007
    ..DESCRIPTION (provided by applicant): In this proposal, we propose to transfer our HTS-ready, florescence based caspases-3/7 assay to identify novel anti-viral drugs against arboviruses infection based on the different host apoptotic ..
  64. AREA: Synthesis and Evaluation of New Cathepsin B, D, and K Inhibitors
    Rose McConnell; Fiscal Year: 2009
    ..drugs have been found to cause a release of cathepsins into the cytosol, which leads to activation of caspases and apoptosis...
  65. Significance of Caspase-Mediated Cleavage of PARP-1 in Cell Death
    KAREN DAVID; Fiscal Year: 2007
    ..One possible form of PARP-1 regulation during apoptotic cell death occurs when active caspases cleave PARP-1 into 89 and 24 kDa fragments possibly leading to PARP-1 inactivation...
  66. GENE REGULATION OF MAMMALIAN DNA VIRUSES
    Richard Moyer; Fiscal Year: 2005
    ..CPV crmA and MYX SERP2 both have Asp at the P1 position, and inhibit similar proteinases (caspases and granzyme B) in vitro...
  67. CASPASES IN RENAL TUBULAR EPITHELIAL CELL INJURY
    GUR KAUSHAL; Fiscal Year: 2000
    b>Caspases (ICE/Ced3 proteases) are a recently identified group of closely related cysteine proteases that play key roles in cell death...
  68. Poxvirus proteins involved in virion binding, membrane fusion, & entry into cells
    Richard Moyer; Fiscal Year: 2007
    ..CPV crmA and MYX SERP2 both have Asp at the PI position, and inhibit similar proteinases (caspases and granzyme B) in vitro...
  69. PATHOGENESIS OF LIVER CELL NECROSIS
    John Farber; Fiscal Year: 2005
    ..Second, apoptosis is characterized by the energy-dependent activation of caspases as a consequence of the MPT...
  70. Dissecting the Molecular Pathway of Aponecrosis
    Junying Yuan; Fiscal Year: 2005
    ..The Specific Aim 1 is to evaluation of the roles of Bcl-xL, caspases and stress kinases in necrotic cell death...
  71. The Mitochondrial Permeabilty Transition in Apoptosis
    Brian Herman; Fiscal Year: 2005
    ..e. cytochrome c) that activate specific class of cysteine proteases (caspases), leading to cell death...
  72. The Role of Caspases in Warm and Cold Ischemia
    ALKESH HARIHAR JANI; Fiscal Year: 2010
    ..This grant will focus on the pathophysiology of cold and warm ischemia and specifically the role of caspases. Caspase-3 is a major mediator of apoptotic and necrotic cell death...
  73. The Role Cellular Metabolism in Regulating Apoptosis
    CAROLINE YI; Fiscal Year: 2009
    ..our identification of several metabolic genes in a genome-wide RNAi screen in fly cells for direct regulators of caspases, 2) our observation that these genes modulate cellular NADPH levels, and 3) recent work from other labs ..