caspase-8

Summary

Gene Symbol: caspase-8
Description: caspase 8
Alias: ALPS2B, CAP4, Casp-8, FLICE, MACH, MCH5, caspase-8, FADD-homologous ICE/CED-3-like protease, FADD-like ICE, ICE-like apoptotic protease 5, MACH-alpha-1/2/3 protein, MACH-beta-1/2/3/4 protein, MORT1-associated ced-3 homolog, apoptotic cysteine protease, apoptotic protease Mch-5, caspase 8, apoptosis-related cysteine peptidase, caspase 8, apoptosis-related cysteine protease
Species: human

Top Publications

  1. ncbi CASH, a novel caspase homologue with death effector domains
    Y V Goltsev
    Department of Membrane Research and Biophysics, Weizmann Institute of Science, 76100 Rehovot, Israel
    J Biol Chem 272:19641-4. 1997
  2. ncbi Rapid cytochrome c release, activation of caspases 3, 6, 7 and 8 followed by Bap31 cleavage in HeLa cells treated with photodynamic therapy
    D J Granville
    QLT PhotoTherapeutics Inc, Department of Pathology and Laboratory Medicine, St Paul s Hospital University of British Columbia, Vancouver, Canada
    FEBS Lett 437:5-10. 1998
  3. pmc Caspase-10 is an initiator caspase in death receptor signaling
    J Wang
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N311, 10 Center Drive, MSC 1892, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 98:13884-8. 2001
  4. ncbi The structure of FADD and its mode of interaction with procaspase-8
    Paul E Carrington
    Laboratory of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, Box 42, New York, New York 10021, USA
    Mol Cell 22:599-610. 2006
  5. pmc Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation
    Young Sik Cho
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Cell 137:1112-23. 2009
  6. doi The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs
    Tencho Tenev
    The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, UK
    Mol Cell 43:432-48. 2011
  7. doi Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a noncanonical caspase-8 inflammasome
    Sonja I Gringhuis
    Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Nat Immunol 13:246-54. 2012
  8. ncbi Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB
    N Inohara
    Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 274:14560-7. 1999
  9. doi Stoichiometry of the CD95 death-inducing signaling complex: experimental and modeling evidence for a death effector domain chain model
    Kolja Schleich
    Division of Immunogenetics, German Cancer Research Center DKFZ, 69120 Heidelberg, Germany
    Mol Cell 47:306-19. 2012
  10. pmc Human immunodeficiency virus type 1 Vpr induces apoptosis in human neuronal cells
    C A Patel
    The Dorrance H Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Virol 74:9717-26. 2000

Research Grants

  1. Caspases, Calpains and Neuronal Cell death
    Stan Krajewski; Fiscal Year: 2006
  2. Programmed necrosis in Immune Responses
    Francis Ka Ming Chan; Fiscal Year: 2013
  3. HOW ENVIRONMENTAL CHEMICALS IMPAIR IMMUNITY
    David Sherr; Fiscal Year: 2009
  4. Engineering tyrosine kinase-activated caspases for selective cancer cell killing
    SALLY A KORNBLUTH; Fiscal Year: 2013
  5. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
  6. C/EBP beta SIGNALS HEPATOCYTE PROLIFERATION AND SURVIVAL
    Mario Chojkier; Fiscal Year: 2012
  7. HTS for Caspase-8 selective TRAIL Sensitizers
    Kristiina Vuori; Fiscal Year: 2013
  8. Guy S Salvesen; Fiscal Year: 2015
  9. Douglas R Green; Fiscal Year: 2016
  10. Peixin Yang; Fiscal Year: 2016

Detail Information

Publications302 found, 100 shown here

  1. ncbi CASH, a novel caspase homologue with death effector domains
    Y V Goltsev
    Department of Membrane Research and Biophysics, Weizmann Institute of Science, 76100 Rehovot, Israel
    J Biol Chem 272:19641-4. 1997
    ..The findings suggest that CASH acts as an attenuator and/or initiator in CD95 and CD120a signaling for cell death...
  2. ncbi Rapid cytochrome c release, activation of caspases 3, 6, 7 and 8 followed by Bap31 cleavage in HeLa cells treated with photodynamic therapy
    D J Granville
    QLT PhotoTherapeutics Inc, Department of Pathology and Laboratory Medicine, St Paul s Hospital University of British Columbia, Vancouver, Canada
    FEBS Lett 437:5-10. 1998
    ..To our knowledge, this is the first example of a chemotherapeutic agent inducing caspase-8 activation and demonstrates that caspase-8 activation can occur after cytochrome c release...
  3. pmc Caspase-10 is an initiator caspase in death receptor signaling
    J Wang
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10, Room 11N311, 10 Center Drive, MSC 1892, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 98:13884-8. 2001
    ..Nonetheless, we find that caspase-8 and -10 may have different apoptosis substrates and therefore potentially distinct roles in death receptor signaling or other cellular processes...
  4. ncbi The structure of FADD and its mode of interaction with procaspase-8
    Paul E Carrington
    Laboratory of Molecular Biophysics, The Rockefeller University, 1230 York Avenue, Box 42, New York, New York 10021, USA
    Mol Cell 22:599-610. 2006
    ..The structure of FADD and its functional characterization, therefore, illustrate the architecture of key components in the death-inducing signaling complex...
  5. pmc Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation
    Young Sik Cho
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    Cell 137:1112-23. 2009
    ..Our findings suggest that RIP3 controls programmed necrosis by initiating the pronecrotic kinase cascade, and that this is necessary for the inflammatory response against virus infections...
  6. doi The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs
    Tencho Tenev
    The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, UK
    Mol Cell 43:432-48. 2011
    ..Together, our observations shed new light on fundamental mechanisms by which chemotherapeutics may kill cancer cells...
  7. doi Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a noncanonical caspase-8 inflammasome
    Sonja I Gringhuis
    Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Nat Immunol 13:246-54. 2012
    ..Thus, dectin-1 acted as an extracellular sensor for pathogens that induced both IL-1β production and maturation through a noncanonical caspase-8-dependent inflammasome for protective immunity...
  8. ncbi Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB
    N Inohara
    Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 274:14560-7. 1999
    ..Thus, Nod1 is a leucine-rich repeat-containing Apaf-1-like molecule that can regulate both apoptosis and NF-kappaB activation pathways...
  9. doi Stoichiometry of the CD95 death-inducing signaling complex: experimental and modeling evidence for a death effector domain chain model
    Kolja Schleich
    Division of Immunogenetics, German Cancer Research Center DKFZ, 69120 Heidelberg, Germany
    Mol Cell 47:306-19. 2012
    ..Taken together, our findings provide an enhanced understanding of caspase-8 activation and initiation of apoptosis at the DISC...
  10. pmc Human immunodeficiency virus type 1 Vpr induces apoptosis in human neuronal cells
    C A Patel
    The Dorrance H Hamilton Laboratories, Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Virol 74:9717-26. 2000
    ..Also, identification of the intracellular activation of caspase-8 in Vpr-induced apoptosis of human neuronal cells may lead to therapeutic approaches which can be used to combat HIV-1-induced neuronal apoptosis in AIDS patients with ADC...
  11. pmc Caspase-8 cleaves its substrates from the plasma membrane upon CD95-induced apoptosis
    J Beaudouin
    Department for Bioinformatics and Functional Genomics, Division of Theoretical Bioinformatics, German Cancer Research Center DKFZ, Institute for Pharmacy and Molecular Biotechnology IPMB and BioQuant, Heidelberg, Germany
    Cell Death Differ 20:599-610. 2013
    ..Subcellular compartmentalization of caspase-8 activity may serve to restrict enzymatic activity before mitochondrial pathway activation and offers new possibilities to interfere with apoptotic sensitivity of the cells...
  12. pmc Genetic polymorphisms of the CASP8 gene promoter may not be associated with colorectal cancer in Han Chinese from southwest China
    Mei Sheng Xiao
    Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, China
    PLoS ONE 8:e67577. 2013
    b>Caspase 8 (CASP8) plays a critical role in the apoptotic pathway and aberrant regulation of this pathway causes many diseases including cancers...
  13. doi Functions of Tat: the versatile protein of human immunodeficiency virus type 1
    Bizhan Romani
    Division of Medical Virology, Department of Pathology, University of Stellenbosch, Tygerberg 7505, South Africa
    J Gen Virol 91:1-12. 2010
    ..Due to its pivotal role in viral replication and in disease pathogenesis, Tat and the cellular pathways targeted by Tat are potential targets for new anti-HIV drugs...
  14. pmc HIV-1 viral protein r induces ERK and caspase-8-dependent apoptosis in renal tubular epithelial cells
    Alexandra Snyder
    Department of Nephrology, Mount Sinai School of Medicine, New York, New York 10029, USA
    AIDS 24:1107-19. 2010
    ..HIV-1 viral protein r (Vpr) has been implicated in HIV-induced RTEC apoptosis but the mechanisms of Vpr-induced RTEC apoptosis are unknown. The aim of this study was therefore to determine the mechanisms of Vpr-induced apoptosis in RTEC...
  15. pmc Following cytochrome c release, autophagy is inhibited during chemotherapy-induced apoptosis by caspase 8-mediated cleavage of Beclin 1
    Hua Li
    Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Cancer Res 71:3625-34. 2011
    ..Induction of autophagy required Beclin 1 and was associated with blockage of Beclin 1 cleavage by caspase 8 at two sites...
  16. pmc TWEAK induces apoptosis through a death-signaling complex comprising receptor-interacting protein 1 (RIP1), Fas-associated death domain (FADD), and caspase-8
    Aminah Ikner
    Department of Molecular Oncology, Genentech, South San Francisco, California 94080, USA
    J Biol Chem 286:21546-54. 2011
    ..The proapoptotic activity of TWEAK is modulated by cIAP1 and CYLD and engages both the extrinsic and intrinsic signaling pathways...
  17. 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...
  18. ncbi Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1
    Jean Antoine Ribeil
    CNRS UMR 8147, Faculté de Médecine et Université René Descartes Paris V, Institut Fédérative Necker, 75270 Paris, France
    Nature 445:102-5. 2007
    ..These effects are abrogated by the transduction of a caspase-resistant GATA-1 mutant. Thus, in erythroid precursors undergoing terminal differentiation, Hsp70 prevents active caspase-3 from cleaving GATA-1 and inducing apoptosis...
  19. ncbi Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death
    A M Chinnaiyan
    University of Michigan Medical School, Department of Pathology, Ann Arbor, MI 48109, USA
    Science 275:1122-6. 1997
    ..simultaneously interact with CED-3 and its mammalian counterparts interleukin-1beta-converting enzyme (ICE) and FLICE. Thus, CED-4 plays a central role in the cell death pathway, biochemically linking CED-9 and the Bcl-2 family to ..
  20. ncbi Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells
    Changjiang Weng
    Center for Molecular Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China 100080
    J Biol Chem 280:10491-500. 2005
    ..These results suggested that removal of N-terminal domains of Bid by caspase-8 and Mcl-1 by caspase-3 enabled the maximal mitochondrial perturbation that potentiated TRAIL-induced apoptosis...
  21. pmc RNA silencing of Mcl-1 enhances ABT-737-mediated apoptosis in melanoma: role for a caspase-8-dependent pathway
    Angela M Keuling
    Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada
    PLoS ONE 4:e6651. 2009
    ..However, overexpression of Mcl-1, a frequent observance in melanoma, is known to confer ABT-737 resistance...
  22. pmc Caspase 8 inhibits programmed necrosis by processing CYLD
    Marie Anne O'Donnell
    Immunology Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nat Cell Biol 13:1437-42. 2011
    b>Caspase 8 initiates apoptosis downstream of TNF death receptors by undergoing autocleavage and processing the executioner caspase 3 (ref. 1)...
  23. ncbi Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi
    Francois G Gervais
    Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire Dorval, Quebec, Canada H9R 4P8
    Nat Cell Biol 4:95-105. 2002
    ..This novel non-receptor-mediated pathway for activating caspase-8 might contribute to neuronal death in Huntington disease...
  24. 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
    ..Thus, Fas, TRAIL and TNF receptors can initiate cell death by two alternative pathways, one relying on caspase-8 and the other dependent on the kinase RIP...
  25. doi Polymorphisms of caspase 8 and caspase 9 gene and colorectal cancer susceptibility and prognosis
    George E Theodoropoulos
    First Propaedeutic Surgical Department, Hippocration University Hospital, 7 Semitelou Street, 11528, Athens, Greece
    Int J Colorectal Dis 26:1113-8. 2011
    ..Our aim was to investigate the association between CASP8 and CASP9 gene polymorphisms and colorectal cancer (CRC) susceptibility...
  26. pmc ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic development
    Shigeru Oshima
    Department of Medicine, University of California at San Francisco, 513 Parnassus Avenue, S 1057, San Francisco, California 94143 0451, USA
    Nature 457:906-9. 2009
    ..ABIN-1 inhibits caspase 8 recruitment to FADD (Fas-associated death domain-containing protein) in TNF-induced signalling complexes, ..
  27. pmc Virion-associated Vpr of human immunodeficiency virus type 1 triggers activation of apoptotic events and enhances fas-induced apoptosis in human T cells
    Hubert Arokium
    Department of Microbiology, Immunology and Molecular Genetics, University of California at Los Angeles, David Geffen School of Medicine, 615 Charles E Young Dr South, BSRB 173, Los Angeles, CA 90095, USA
    J Virol 83:11283-97. 2009
    ..In contrast to a previous study, we also detected the activation of caspase 8, the initiator caspase of the death receptor pathway...
  28. pmc The caspase-8 dimerization/dissociation balance is a highly potent regulator of caspase-8, -3, -6 signaling
    Maximilian L Würstle
    Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland
    J Biol Chem 285:33209-18. 2010
    ..Our study therefore highlights a central and so far underappreciated role of caspase-8 dimerization/dissociation in avoiding unwanted cell death by lethal amplification of caspase responses via the caspase-8, -3, -6 loop...
  29. pmc FLASH links the CD95 signaling pathway to the cell nucleus and nuclear bodies
    Kristijana Milovic-Holm
    Heinrich Pette Institut für Experimentelle Virologie und Immunologie, Hamburg, Germany
    EMBO J 26:391-401. 2007
    Caspase-8-binding protein FLICE-associated huge protein (FLASH) has been proposed to regulate death receptor CD95-induced apoptosis through facilitating caspase-8 activation at the death-inducing signaling complex...
  30. pmc Death effector domain DEDa, a self-cleaved product of caspase-8/Mch5, translocates to the nucleus by binding to ERK1/2 and upregulates procaspase-8 expression via a p53-dependent mechanism
    Zhan Yao
    Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People s Republic of China
    EMBO J 26:1068-80. 2007
    ..Here, we demonstrate that the prodomain of the caspase-8/Mch5 can be further cleaved between two tandemly repeated DEDs (DEDa-DEDb) at the amino-acid residue Asp129 by caspase-8 ..
  31. ncbi Caspase-1 and caspase-8 cleave and inactivate cellular parkin
    Soren Kahns
    Department of Molecular Biology, University of Aarhus, DK 8000 Aarhus C, Denmark
    J Biol Chem 278:23376-80. 2003
    ....
  32. ncbi Characterization of caspase-8L: a novel isoform of caspase-8 that behaves as an inhibitor of the caspase cascade
    Daisuke Himeji
    Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Japan
    Blood 99:4070-8. 2002
    Caspase-8 (Fas-associating protein with death domain-like interleukin-1beta- converting enzyme [FLICE]/MACH/Mch5) belongs to a family of cysteine proteases presumed to be the apex of the apoptotic signaling pathways...
  33. ncbi Expression of short-form caspase 8 correlates with decreased sensitivity to Fas-mediated apoptosis in neuroblastoma cells
    Rodrick R Kisenge
    Department of Pediatrics, Mie University School of Medicine, Tsu, Mie 514 8507, Japan
    Cancer Sci 94:598-605. 2003
    ..b>Caspase 8, one of the initiator caspases, plays an important role in the Fas-Fas ligand pathway...
  34. ncbi Caspase-8 gene expression in neuroblastoma
    Ida Casciano
    Laboratory of Tumor Genetics, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi 10, 16132 Genova, Italy
    Ann N Y Acad Sci 1028:157-67. 2004
    ..Our results provide new insights to the regulation of CASP8, a gene with an essential role in a variety of physiologic and pathologic conditions...
  35. pmc Palmitoylation of CD95 facilitates formation of SDS-stable receptor aggregates that initiate apoptosis signaling
    Christine Feig
    The Ben May Institute for Cancer Research, University of Chicago, Chicago, IL 60637, USA
    EMBO J 26:221-31. 2007
    ..Our data demonstrate that SDS-stable forms of CD95 are the sites of apoptosis initiation and represent an important early step in apoptosis signaling through CD95 before activation of caspases...
  36. doi Caspase 9 and caspase 8 gene polymorphisms and susceptibility to bladder cancer in north Indian population
    Ruchika Gangwar
    Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
    Ann Surg Oncol 16:2028-34. 2009
    Dysregulation of apoptosis plays a crucial role in carcinogenesis. Our aim was to investigate the association of Caspase 9 and Caspase 8 gene polymorphism with bladder cancer (BC) susceptibility.
  37. doi CASP8 -652 6N del polymorphism and cancer risk: a meta-analysis of 30 case-control studies in 50,112 subjects
    Fan Zhang
    Department of Maternal and Child Health, School of Public Health and Health Management, Chongqing Medical University, Chongqing 400016, China
    Mutagenesis 27:559-66. 2012
    ..However, further research, such as studies focusing on additional ethnic groups and cancer types, is needed to provide a more exact and comprehensive synthesis conclusion...
  38. ncbi Dominant expression of a novel splice variant of caspase-8 in human peripheral blood lymphocytes
    T Horiuchi
    Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
    Biochem Biophys Res Commun 272:877-81. 2000
    ..In patients with systemic lupus erythematosus (SLE), imbalanced expression of caspase-8L transcript was identified. These results suggest the important role of caspase-8L in the modulation of apoptosis...
  39. doi The CASP8 -652 6N insertion/deletion promoter polymorphism is associated with renal cell carcinoma risk and metastasis
    Michela de Martino
    Departments of Urology and Clinical Pathology AH, Medical University of Vienna, Vienna, Austria
    J Urol 190:717-22. 2013
    ..We studied the association of this polymorphism with renal cell carcinoma risk and pathology...
  40. doi Polymorphisms in the promoter region of the CASP8 gene are not associated with non-Hodgkin's lymphoma in Chinese patients
    Mei Sheng Xiao
    Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China
    Ann Hematol 90:1137-44. 2011
    ..Our negative results gave no support for an active role for these genetic variants in conferring NHL in Chinese patients...
  41. ncbi Recruitment of TNF receptor 1 to lipid rafts is essential for TNFalpha-mediated NF-kappaB activation
    Daniel F Legler
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, CH 1066 Epalinges, Switzerland
    Immunity 18:655-64. 2003
    ..We suggest that lipid rafts are crucial for the outcome of TNFalpha-activated signaling pathways...
  42. pmc Association of polymorphisms in CASP10 and CASP8 with FEV(1)/FVC and bronchial hyperresponsiveness in ethnically diverse asthmatics
    Alicia K Smith
    Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA
    Clin Exp Allergy 38:1738-44. 2008
    ..These genes regulate the extrinsic apoptosis pathway utilized by several types of immune and structural cells that have been implicated in the pathogenesis of asthma...
  43. pmc Glucocorticoid-induced activation of caspase-8 protects the glucocorticoid-induced protein Gilz from proteasomal degradation and induces its binding to SUMO-1 in murine thymocytes
    D V Delfino
    Section of Pharmacology Toxicology and Chemotherapy, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy
    Cell Death Differ 18:183-90. 2011
    ..In summary, our results suggest that caspase-8 activation protects Gilz from proteasomal degradation and induces its binding to SUMO-1 in GC-treated thymocytes...
  44. doi Single-cell analysis of dihydroartemisinin-induced apoptosis through reactive oxygen species-mediated caspase-8 activation and mitochondrial pathway in ASTC-a-1 cells using fluorescence imaging techniques
    Ying Ying Lu
    South China Normal University, Institute of Laser Life Science, MOE Key Laboratory of Laser Life Science, Guangzhou, China
    J Biomed Opt 15:046028. 2010
    ....
  45. pmc Polymorphism in tumor necrosis factor-related apoptosis-inducing ligand receptor 1 is associated with poor viral response to interferon-based hepatitis C virus therapy in HIV/hepatitis C virus-coinfected individuals
    Stacey A Rizza
    Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    AIDS 24:2639-44. 2010
    ..There are currently no biomarkers that predict treatment response in these coinfected patients...
  46. pmc Inhibition of protein degradation induces apoptosis through a microtubule-associated protein 1 light chain 3-mediated activation of caspase-8 at intracellular membranes
    Ji An Pan
    Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794 5222, USA
    Mol Cell Biol 31:3158-70. 2011
    ..Our results unveiled a previously unknown mechanism through which disruption of protein homeostasis induces caspase-8 oligomerization, activation, and apoptosis...
  47. pmc Smad7 protein induces interferon regulatory factor 1-dependent transcriptional activation of caspase 8 to restore tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis
    Suntaek Hong
    Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 406 840, Republic of Korea
    J Biol Chem 288:3560-70. 2013
    ..By screening differentially regulated genes, we found that the caspase 8 gene was highly up-regulated in Smad7-expressing cells...
  48. pmc IL-6 cytoprotection in hyperoxic acute lung injury occurs via suppressor of cytokine signaling-1-induced apoptosis signal-regulating kinase-1 degradation
    Narasaiah Kolliputi
    Pulmonary Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Bulfinch 148, Boston, MA 02114, USA
    Am J Respir Cell Mol Biol 40:314-24. 2009
    ..Furthermore, the interaction between SOCS-1 and ASK-1 promotes ubiquitin-mediated degradation both in vivo and in vitro. These studies demonstrate that SOCS-1 is an important regulator in IL-6-induced cytoprotection against HALI...
  49. doi Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition
    Sai Mun Leong
    Department of Biological Sciences, National University of Singapore, Singapore
    Blood 116:3286-96. 2010
    ..Our data hence provide a potential explanation for the myeloid-specific involvement of cytoplasmic NPM in the leukemogenesis of a large subset of acute myeloid leukemia...
  50. pmc Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-dependent manner but can not functionally substitute caspase-8
    Martin R Sprick
    Division for Apoptosis Regulation, Tumour Immunology Program, DKFZ, Heidelberg, Germany
    EMBO J 21:4520-30. 2002
    ..Finally, we demonstrate that caspase-10 is cleaved during CD95-induced apoptosis of activated T cells. These results show that caspase-10 activation occurs in primary cells, but that its function differs from that of caspase-8...
  51. ncbi Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain
    V Cowling
    Signal Transduction Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Cell Death Differ 9:1046-56. 2002
    ..We suggest that the requirement for two distinct cleavage steps to activate an effector caspase may represent an effective mechanism for restriction of spontaneous caspase activation and aberrant entry into apoptosis...
  52. pmc Cardiolipin provides an essential activating platform for caspase-8 on mitochondria
    Francois Gonzalvez
    Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow, Scotland, UK
    J Cell Biol 183:681-96. 2008
    ....
  53. pmc Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activation
    Andrew Oberst
    Department of Immunology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 285:16632-42. 2010
    ....
  54. ncbi The CASP8 -652 6N del promoter polymorphism and breast cancer risk: a multicenter study
    Bernd Frank
    Helmholtz University Group Molecular Epidemiology, German Cancer Research Center, DKFZ, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany
    Breast Cancer Res Treat 111:139-44. 2008
    ..The combined per allele odds ratio (OR) was 0.97 (95% confidence interval (CI), 95% CI = 0.93-1.02). The present result indicates that the CASP8 -652 6N del variant has no significant effect on BC risk in Europeans...
  55. ncbi HIV-1 protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload, and oxidative stress
    I I Kruman
    Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, 40536, USA
    Exp Neurol 154:276-88. 1998
    ..Agents that interupt this apoptotic cascade may prove beneficial in preventing neuronal degeneration and associated dementia in AIDS patients...
  56. ncbi The up-regulation of human caspase-8 by interferon-gamma in breast tumor cells requires the induction and action of the transcription factor interferon regulatory factor-1
    Carmen Ruiz-Ruiz
    Instituto de Parasitologia y Biomedicina, CSIC, Calle Ventanilla 11, 18001 Granada, Centro de Biologia Molecular Severo Ochoa, Universidad Autonoma de Madrid, Madrid E 28049, Spain
    J Biol Chem 279:19712-20. 2004
    ..These data define a new pathway through which IFN-gamma might control the sensitivity of tumor cell to death receptor-mediated apoptosis...
  57. ncbi Suppression of extracellular signal-related kinase and activation of p38 MAPK are two critical events leading to caspase-8- and mitochondria-mediated cell death in phytosphingosine-treated human cancer cells
    Moon Taek Park
    Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul 139 706, Korea
    J Biol Chem 278:50624-34. 2003
    ..Molecular dissection of the signaling pathways that activate the apoptotic cell death machinery is critical for both our understanding of cell death events and development of cancer therapeutic agents...
  58. pmc Cellular FLICE-inhibitory protein (cFLIP) isoforms block CD95- and TRAIL death receptor-induced gene induction irrespective of processing of caspase-8 or cFLIP in the death-inducing signaling complex
    Shyam M Kavuri
    Department of Dermatology and Venereology, Laboratory for Experimental Dermatology, Otto von Guericke University Magdeburg, Magdeburg 39120, Germany
    J Biol Chem 286:16631-46. 2011
    ..cFLIP-mediated inhibition of CD95 and TRAIL DR could be of crucial importance during keratinocyte skin carcinogenesis and for the activation of innate and/or adaptive immune responses triggered by DR activation in the skin...
  59. pmc A CASP-8 mutation recognized by cytolytic T lymphocytes on a human head and neck carcinoma
    S Mandruzzato
    Ludwig Institute for Cancer Research, Brussels Branch, and Unité de Génétique Cellulaire, Universite Catholique de Louvain, B 1200 Brussels, Belgium
    J Exp Med 186:785-93. 1997
    ..The antigen is encoded by a mutated form of the CASP-8 gene. This gene, also named FLICE or MACH, codes for protease caspase-8, which is required for induction of apoptosis through the Fas receptor and ..
  60. pmc Identification of the cytolinker plectin as a major early in vivo substrate for caspase 8 during CD95- and tumor necrosis factor receptor-mediated apoptosis
    A H Stegh
    Tumor Immunology Program, German Cancer Research Center, D 69120 Heidelberg, Germany
    Mol Cell Biol 20:5665-79. 2000
    b>Caspase 8 plays an essential role in the execution of death receptor-mediated apoptosis...
  61. pmc CASP8 polymorphisms contribute to cancer susceptibility: evidence from a meta-analysis of 23 publications with 55 individual studies
    Ming Yin
    Department of Epidemiology, The University of Texas, M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Carcinogenesis 31:850-7. 2010
    Several potentially functional polymorphisms of CASP8 encoding an apoptotic enzyme, caspase 8, have been implicated in cancer risk, but individually published studies showed inconclusive results...
  62. 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...
  63. pmc Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation
    Y Hu
    Departments of Pathology and Comprehensive Cancer Center, 1500 East Medical Center Drive, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 95:4386-91. 1998
    ..These experiments demonstrate that Bcl-XL associates with caspase-9 and Apaf-1, and show that Bcl-XL inhibits the maturation of caspase-9 mediated by Apaf-1, a process that is evolutionarily conserved from nematodes to humans...
  64. pmc Human immunodeficiency virus type 1 Tat induces apoptosis and increases sensitivity to apoptotic signals by up-regulating FLICE/caspase-8
    S R Bartz
    Divisions of Molecular Medicine and Basic Science, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
    J Virol 73:1956-63. 1999
    ..The up-regulation of casp-8 by HIV-1 Tat expression may contribute to the increased apoptosis and sensitivity to apoptotic signals observed in the cells of HIV-1-infected persons...
  65. ncbi HIV-1 Vpr induces apoptosis through caspase 9 in T cells and peripheral blood mononuclear cells
    Karuppiah Muthumani
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 277:37820-31. 2002
    ..Furthermore, we observed that with both vectors, caspase 9, but not caspase 8, was activated following infection of human peripheral blood mononuclear cell with either Vpr-positive HIV ..
  66. ncbi Interferon-gamma differentially regulates monocyte matrix metalloproteinase-1 and -9 through tumor necrosis factor-alpha and caspase 8
    Min Zhou
    Immunopathology Section, NIDCR, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 278:45406-13. 2003
    ..In contrast to its effects on MMP-1, IFNgamma inhibited TNFalpha-induced MMP-9 through a caspase 8-dependent pathway as demonstrated by the restoration of MMP-9 with caspase 8 inhibitors...
  67. ncbi The Siva protein is a novel intracellular ligand of the CD4 receptor that promotes HIV-1 envelope-induced apoptosis in T-lymphoid cells
    Bénédicte Py
    Institut Cochin, CNRS UMR 8104, Universite Paris Descartes, 27 rue du Faubourg Saint Jacques, 75014, Paris, France
    Apoptosis 12:1879-92. 2007
    ..Altogether, these results suggest that Siva-1 might participate in the CD4-initiated signaling apoptotic pathway induced by the HIV-1 envelope in T-lymphoid cells...
  68. ncbi Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency
    Hyung J Chun
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 419:395-9. 2002
    ..Thus, caspase-8 deficiency in humans is compatible with normal development and shows that caspase-8 has a postnatal role in immune activation of naive lymphocytes...
  69. ncbi Caspase-8 interacts with the p85 subunit of phosphatidylinositol 3-kinase to regulate cell adhesion and motility
    Jamie Senft
    Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia 26506, USA
    Cancer Res 67:11505-9. 2007
    ..These results suggest that caspase-8 phosphorylation converts it from a proapoptotic factor to a cell motility factor that, through tyrosine-380, interacts with p85, an established cell migration component...
  70. ncbi Association of the CASP10 V410I variant with reduced familial breast cancer risk and interaction with the CASP8 D302H variant
    Bernd Frank
    Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany
    Carcinogenesis 27:606-9. 2006
    ..35, P(trend) = 0.007), pointing to the interaction between the CASP10 and CASP8 polymorphisms in breast carcinogenesis...
  71. ncbi Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death
    M P Boldin
    Department of Membrane Research and Biophysics, The Weizmann Institute of Science, Rehovot, Israel
    Cell 85:803-15. 1996
    ..MORT1 and TRADD can also bind to each other. We have cloned a novel protein, MACH, that binds to MORT1...
  72. ncbi FLICE induced apoptosis in a cell-free system. Cleavage of caspase zymogens
    M Muzio
    Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 272:2952-6. 1997
    ..both CD95 and TNFR-1 death receptors initiate apoptosis by recruiting a novel ICE/CED-3 family member, designated FLICE/MACH, to the receptor signaling complex...
  73. ncbi Activation of the NF-kappaB pathway by caspase 8 and its homologs
    P M Chaudhary
    Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, Texas, TX 75390 8593, USA
    Oncogene 19:4451-60. 2000
    b>Caspase 8 is the most proximal caspase in the caspase cascade and has been known for its role in the mediation of cell death by various death receptors belonging to the TNFR family...
  74. ncbi Differential inactivation of caspase-8 in lung cancers
    Narayan Shivapurkar
    Hamon Center for Therapeutic Oncology Research, Departments of Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, Texas 75390 8593, USA
    Cancer Biol Ther 1:65-9. 2002
    ..CASP8 may function as a tumor suppressor gene in neuroendocrine lung tumors...
  75. ncbi Silencing of death receptor and caspase-8 expression in small cell lung carcinoma cell lines and tumors by DNA methylation
    S Hopkins-Donaldson
    University Hospital Zurich, Switzerland
    Cell Death Differ 10:356-64. 2003
    ..These results suggest that SCLC cells are highly resistant to apoptosis mediated by death receptors and that this resistance can be reduced by a combination of demethylation and treatment with IFNgamma...
  76. ncbi Amplification of CD95 activation by caspase 8-induced endosomal acidification in rat hepatocytes
    Roland Reinehr
    Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich Heine University Dusseldorf, D 40225 Dusseldorf, Germany
    J Biol Chem 283:2211-22. 2008
    ..Interestingly, caspase 8 inhibitors abolished these CD95L-induced signaling events, including the increase in cytosolic [Cl(-)], ..
  77. doi Mutational analysis of CASP1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 14 genes in gastrointestinal stromal tumors
    Yoo Ri Kim
    Department of Pathology, The Catholic University of Korea, Seoul, Korea
    Hum Pathol 40:868-71. 2009
    ....
  78. ncbi Casper is a FADD- and caspase-related inducer of apoptosis
    H B Shu
    Tularik, Incorporated, South San Francisco, California 94080, USA
    Immunity 6:751-63. 1997
    ..When overexpressed in mammalian cells, Casper potently induces apoptosis. A C-terminal deletion mutant of Casper inhibits TNF- and Fas-induced cell death, suggesting that Casper is involved in these apoptotic pathways...
  79. pmc p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum
    F W Ng
    Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, Quebec, Canada H3G 1Y6
    J Cell Biol 139:327-38. 1997
    ..In cotransfected 293T cells, p28 is part of a complex that includes Bcl-2/Bcl-XL and procaspase-8 (pro-FLICE)...
  80. 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...
  81. ncbi Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha-induced apoptosis
    D Kitsberg
    Harvard Medical School, Boston, Massachusetts 02115, USA
    J Neurosci 19:8244-51. 1999
    ..After generation of PEA-15 null mutant mice, our results demonstrate that PEA-15 expression increases astrocyte survival after exposure to TNF...
  82. ncbi Inactivation of caspase-8 on mitochondria of Bcl-xL-expressing MCF7-Fas cells: role for the bifunctional apoptosis regulator protein
    Alexander H Stegh
    Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 277:4351-60. 2002
    ....
  83. pmc The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at the endoplasmic reticulum
    David G Breckenridge
    Department of Biochemistry, McIntyre Medical Sciences Building, McGill University, Montreal, QC, Canada H3G 1Y6
    Proc Natl Acad Sci U S A 99:4331-6. 2002
    ..Preferential recruitment of procaspase-8L by the BAP31 complex at the endoplasmic reticulum suggests an additional pathway for regulating initiator caspase-8 during apoptosis...
  84. ncbi TRAIL receptor and CD95 signal to mitochondria via FADD, caspase-8/10, Bid, and Bax but differentially regulate events downstream from truncated Bid
    Arlette B Werner
    Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    J Biol Chem 277:40760-7. 2002
    ..We conclude that the TRAIL receptor can bypass or neutralize the activity of cytosolic factor that blocks truncated Bid function. This may benefit the capacity of TRAIL to break apoptosis resistance in tumor cells...
  85. ncbi A unified model for apical caspase activation
    Kelly M Boatright
    The Program in Apoptosis and Cell Death Research, Burnham Institute, 10901 North Torrey Pines Road, University of California, San Diego, La Jolla, CA 92037, USA
    Mol Cell 11:529-41. 2003
    ..We propose a unified caspase activation hypothesis whereby apical caspases are activated by dimerization of monomeric zymogens...
  86. ncbi Paclitaxel-induced apoptosis in BJAB cells proceeds via a death receptor-independent, caspases-3/-8-driven mitochondrial amplification loop
    Clarissa von Haefen
    Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charite, University of Berlin, Germany
    Oncogene 22:2236-47. 2003
    ..In addition, this is the first report to demonstrate death receptor-independent caspase-8 autoprocessing in vivo...
  87. ncbi Fas-associated factor 1, FAF1, is a member of Fas death-inducing signaling complex
    Seung Wook Ryu
    Research Center for Biomedicinal Resources and Division of Life Science, Paichai University, Daejeon 302 735, Korea
    J Biol Chem 278:24003-10. 2003
    ..Collectively, our data show that FAF1 is a member of Fas-DISC acting upstream of caspase-8...
  88. ncbi Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis
    Nicholas Harper
    Medical Research Council Toxicology Unit, Hodgkin Building, University of Leicester, P O Box 138, Lancaster Road, Leicester, LE1 9HN, United Kingdom
    J Biol Chem 278:25534-41. 2003
    ....
  89. ncbi The human caspase-8 promoter sustains basal activity through SP1 and ETS-like transcription factors and can be up-regulated by a p53-dependent mechanism
    Christian Liedtke
    Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, D 30625 Hannover, Germany
    J Biol Chem 278:27593-604. 2003
    Caspase-8, also known as MACH/FLICE/Mch5, is the most upstream-located cysteine-aspartyl-protease (caspase) in a caspase cascade involved in apoptosis triggered by members of the tumor necrosis factor receptor superfamily or other ..
  90. ncbi Caspase 8-mediated cleavage of the pro-apoptotic BCL-2 family member BID in p53-dependent apoptosis
    Barbara Fischer
    Laboratoire de Cancérologie Expérimentale et de Radiobiologie EA 3430, Universite Louis Pasteur, Institut de Recherche contre les Cancers de l Appareil Digestif, Strasbourg, France
    Biochem Biophys Res Commun 306:516-22. 2003
    ..p53-dependent apoptosis was associated with the activation of caspase 9, 8, 3, and 7 and the cleavage of BID by caspase 8. In contrast, the slow-occurring p53-independent apoptotic process, mediated by caspase 7, took place without ..
  91. pmc Interdimer processing mechanism of procaspase-8 activation
    David W Chang
    Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    EMBO J 22:4132-42. 2003
    ..These results reveal the key steps leading to the activation of procaspase-8 by oligomerization...
  92. pmc Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk in etoposide-induced cell death
    Dhyan Chandra
    Dept of Carcinogenesis, University of Texas M D Anderson Cancer Center, Science Park Research Division, Park Rd 1C, Smithville, TX 78957, USA
    Mol Cell Biol 24:6592-607. 2004
    ..Chandra and D. G. Tang, J. Biol. Chem.278:17408-17420, 2003). We now show that active caspase 8 also becomes associated with the membranes in apoptosis caused by multiple stimuli...
  93. ncbi A common coding variant in CASP8 is associated with breast cancer risk
    Angela Cox
    Sheffield University Medical School, Sheffield S10 2RX, UK
    Nat Genet 39:352-8. 2007
    ..02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies...
  94. ncbi A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancers
    Tong Sun
    Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    Nat Genet 39:605-13. 2007
    ..These results support the hypothesis that genetic variants influencing immune status modify cancer susceptibility...
  95. ncbi Novel noncatalytic role for caspase-8 in promoting SRC-mediated adhesion and Erk signaling in neuroblastoma cells
    Darren Finlay
    Cancer Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Cancer Res 67:11704-11. 2007
    ..This protein complex association of caspase-8 and Src, and concomitant downstream signaling events, may help reconcile why a potential tumor suppressor such as caspase-8 is rarely absent in cancers...
  96. ncbi Mutation of a self-processing site in caspase-8 compromises its apoptotic but not its nonapoptotic functions in bacterial artificial chromosome-transgenic mice
    Tae Bong Kang
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
    J Immunol 181:2522-32. 2008
    ....
  97. doi Clinicopathological significance of caspase-8 and caspase-10 expression in rectal cancer
    Bing Xu
    Department of General Surgery, Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
    Oncology 74:229-36. 2008
    ..To investigate the expression of caspase-8 and -10 in rectal adenoma, adenocarcinoma and the corresponding normal mucosa tissue, and to clarify the relationship between their expression and clinicopathological parameters of rectal cancer...
  98. pmc Caspase 8 promotes peripheral localization and activation of Rab5
    Vicente A Torres
    Department of Pathology, University of California San Diego School of Medicine and the UCSD Moores Cancer Center, La Jolla, California 92093 0803, USA
    J Biol Chem 283:36280-9. 2008
    b>Caspase 8 is a cysteine protease that initiates apoptotic signaling via the extrinsic pathway in a manner dependent upon association with early endosomes...
  99. pmc Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a pooled analysis of 3 population-based case-control studies
    Qing Lan
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA
    Blood 114:264-7. 2009
    ..It is noteworthy that genetic variants in CASP8 were associated with risk of all major NHL subtypes. Our findings suggest that genetic variation in caspases may play an important role in lymphomagenesis...
  100. pmc Critical role for caspase-8 in epidermal growth factor signaling
    Darren Finlay
    Cancer Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Cancer Res 69:5023-9. 2009
    ..As the EGF/Src pathway activity has been shown to promote oncogenic events, our findings that caspase-8 is necessary for these activities may help explain why it is rarely deleted or silenced in tumors...
  101. doi Association of selected polymorphisms of CCND1, p21, and caspase8 with colorectal cancer risk
    Bing Liu
    Department of Epidemiology and Health Statistics, Zhejiang University, Hangzhou, China
    Mol Carcinog 49:75-84. 2010
    ..25). Our findings suggest that the selected polymorphisms of p21, CCND1, and caspase8 may not contribute to the risk of colorectal cancer...

Research Grants74

  1. Caspases, Calpains and Neuronal Cell death
    Stan Krajewski; Fiscal Year: 2006
    ..These animals and cells derived from them will then be used for determining the importance of these proteases for neuronal cell death induced by cerebral ischemia and in certain neurodegenerative diseases. ..
  2. Programmed necrosis in Immune Responses
    Francis Ka Ming Chan; Fiscal Year: 2013
    ..is bolstered by the identification of viral inhibitors against programmed necrosis, such as certain viral FLIPs (FLICE(caspase-8)-like inhibitor proteins) and the mouse cytomegalovirus (MCMV) M45 protein...
  3. HOW ENVIRONMENTAL CHEMICALS IMPAIR IMMUNITY
    David Sherr; Fiscal Year: 2009
    ....
  4. Engineering tyrosine kinase-activated caspases for selective cancer cell killing
    SALLY A KORNBLUTH; Fiscal Year: 2013
    ..Although caspases (such as caspase 8) can be activated in a fairly direct manner by receptor binding of extracellular "death ligands" such as Fas and ..
  5. NIH Director's Pioneer Award
    Junying Yuan; Fiscal Year: 2009
    ..No Abstract provided ..
  6. C/EBP beta SIGNALS HEPATOCYTE PROLIFERATION AND SURVIVAL
    Mario Chojkier; Fiscal Year: 2012
    ..C/EBPI3Glu 2_zmutant blocks hepatocyte apoptosis initiated by death receptors or proteasome inhibitors (FAS/caspase 8 pathway). The specific aims of this proposal are to assess: 1...
  7. HTS for Caspase-8 selective TRAIL Sensitizers
    Kristiina Vuori; Fiscal Year: 2013
    ..Additionally, such agents can be used as tool compounds to further characterize and study cellular survival and death pathways that are differentially regulated in normal and cancer cells. ..
  8. Guy S Salvesen; Fiscal Year: 2015
    ....
  9. Douglas R Green; Fiscal Year: 2016
    ....
  10. Peixin Yang; Fiscal Year: 2016
    ..Our published data in caspase 8 and JNK2, preliminary data in amelioration of diabetic embryopathy by Foxo3a deficiency and preventive effect of ..
  11. AIMALIE LYNNETTE HARDAWAY; Fiscal Year: 2014
    ..Ultimately, these studies should lead to identification of novel signaling pathways and molecular mechanisms predisposing prostate cells to metastasize to bone. ..
  12. Novel Fas/CD95 Signaling Mechanisms
    Marcus E Peter; Fiscal Year: 2011
    ..These studies will provide a basis for understanding the different signaling activities of Fas and to devise new therapeutic approaches for interfering with dysregulated Fas signaling in cancer and other diseases. ..
  13. EOSINOPHIL APOPTOSIS IN ASTHMA
    Gerald Litwack; Fiscal Year: 2001
    ..Furthermore, manipulation of these pathways will be a key area for therapeutic intervention in asthma. ..
  14. Non-apoptotic functions of caspases
    STEVEN MILES FRISCH; Fiscal Year: 2012
    ..It is important to understand the ramifications of this novel function of caspase-8 for oncogenesis and the treatment of human cancer. ..
  15. Cathepsin L in the Biosynthesis of Enkephalins and beta-Endorphin Opioid Peptides
    Steven J Bark; Fiscal Year: 2012
    ....
  16. Fayyaz S Sutterwala; Fiscal Year: 2014
    ..In addition the information gained from the proposed studies will also shed light on the pathogenesis of other fungal organisms. ..
  17. Stephen J Davies; Fiscal Year: 2014
    ....
  18. Dietmar W Siemann; Fiscal Year: 2016
    ....
  19. Telomerase Specific Caspase Transfer for Gliomas
    Seiji Kondo; Fiscal Year: 2004
    ..We anticipate that the studies described in the current proposal will lead to a novel and promising targeting approach for malignant gliomas expressing telomerase activity. ..
  20. The Role of Caspase-8 in Alzheimer's Disease
    Troy Rohn; Fiscal Year: 2001
    ....
  21. JEREMY KODANKO; Fiscal Year: 2016
    ..Literature data confirm that photodynamic therapy is effective against bone tumors in live animal models, which strongly supports our studies. ..
  22. Ethan A Lerner; Fiscal Year: 2014
    ..The results of this project may lead to the development of new drugs to treat itch. ..
  23. Controlled expression of a cystatin C-peptide as therapy for Alzheimer's disease
    PHYLLIS ANN SHAW; Fiscal Year: 2012
    ....
  24. 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. ..
  25. Li Gan; Fiscal Year: 2014
    ..Confirmation that the CatB-CysC axis action acts in a complementary manner with NEP would lay the foundation for designing effective Abeta clearance strategies. ..
  26. Development of protease inhibitor drugs to treat Alzheimer's disease
    GREGORY R HOOK; Fiscal Year: 2010
    ..Currently, there is no effective means of stopping the progress of this devastating disease and there is an urgent need for new drugs that do so. This project may result in drugs that halt or, possibly, reverse the progression of AD. ..
  27. CLIFFORD RUSSELL GREYSON; Fiscal Year: 2016
    ..Agents with potential clinical utility will be identified using the isolated papillary muscle model and tested in the pig model. ..
  28. 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. ..
  29. Wei Xing Zong; Fiscal Year: 2016
    ..At the clinical level, it may establish LC3 or SCCA1 as a molecular signature for suggesting treatment with proteotoxic agents. ..
  30. 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. ..
  31. 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. ..
  32. Gabriel Nunez; Fiscal Year: 2015
    ..These studies may lead to better understanding of mechanisms that control host defense against human pathogens and the pathogenesis of inflammatory disease. ..
  33. Xiang Jin Meng; Fiscal Year: 2016
    ..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. ..
  34. Richard C Condit; Fiscal Year: 2014
    ....
  35. 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. ..
  36. Vishwa Deep Dixit; Fiscal Year: 2014
    ....
  37. Richard B Cooley; Fiscal Year: 2014
    ..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. ..
  38. 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. ..
  39. 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. ..
  40. Gabriel Nunez; Fiscal Year: 2016
    ..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. ..
  41. 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. ..
  42. 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. ..
  43. Repression of inflammasome by Francisella tularensis
    Meenakshi Malik; Fiscal Year: 2013
    ..This proposal is a step ahead in understanding the immunopathogenesis of tularemia. ..
  44. Timothy Tellinghuisen; Fiscal Year: 2014
    ....
  45. 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. ..
  46. 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. ..
  47. Caroline A Genco; Fiscal Year: 2016
    ..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. ..
  48. 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. ..
  49. 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. ..
  50. Dysregulation of ubiquitination in MALT lymphomas
    Xiaolu Yang; Fiscal Year: 2010
    ....
  51. Neural Mechanisms of Itch
    ROBERT H LA MOTTE; Fiscal Year: 2013
    ..abstract_text> ..
  52. 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. ..
  53. James J Havranek; Fiscal Year: 2016
    ..Preliminary results demonstrate that these aims are feasible. Completion of this research will move next-generation protein sequencing much closer to being a reality. ..
  54. Michael J Federle; Fiscal Year: 2015
    ..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. ..
  55. 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. ..
  56. Identifying Calpain-10 Substrates from Human Proteome
    Rihe Liu; Fiscal Year: 2005
    ..abstract_text> ..
  57. 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]..
  58. 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. ..
  59. 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. ..
  60. BIOLOGICAL Function of the Retinoblastoma Gene Product
    Jean Y J Wang; Fiscal Year: 2012
    ..Results from the proposed research will facilitate the development of new strategies to reduce the risk of inflammation-associated cancer. ..
  61. IRA A TABAS; Fiscal Year: 2016
    ..originating from the mitochondria, referred to as "mitoOS," plays a key upstream role and that a novel Bax/Bak-caspase 8 (casp8) pathway plays a major downstream role in advanced lesional Mf apoptosis and plaque necrosis...
  62. Pro-apoptotic BID in DNA Damage and Leukemogenesis
    Sandra S Zinkel; Fiscal Year: 2011
    ..Cleavage by caspase 8 and myristoylation serve to activate BID, facilitating targeting to the mitochondria where it activates ..
  63. Apoptosis and Trophoblast Fusion
    NEAL STEWART ROTE; Fiscal Year: 2010
    ..that villous cytotrophoblast fusion results from aborted activation of apoptotic pathways, particularly through caspase 8-mediated PS efflux...
  64. John J Krolewski; Fiscal Year: 2016
    ..Finally, Aim 3 tests the functional role of FLIP, determining if FLIP down-regulation can cooperate with pro- apoptotic cytokines to induce apoptosis and regression of normal prostate and PrCa in a murine model. ..
  65. The Role of Caspase-8 in Neuroblastoma Tumorigenesis
    GERARD PAUL ZAMBETTI; Fiscal Year: 2013
    ..The studies in this proposal are designed to determine the role of caspase-8 and N-myc, two proteins whose expression is altered in neuroblastoma, in tumorigenesis, metastasis and chemotherapeutic responsiveness. ..
  66. Dwayne G Stupack; Fiscal Year: 2014
    b>Caspase 8 and Integrins in Tumor Progression During the previous funding period, we demonstrated that caspase 8 association with unligated integrins in vivo promoted apoptosis, and that down-regulation of caspase 8 or integrins in ..
  67. Elucidating the Fas-activated inflammation-signaling complex (FISC)
    Mihail Iordanov; Fiscal Year: 2013
    ..characterization of FISC demonstrates the essential roles of the adaptor protein FADD and the initiator caspase 8 (CASP8) which are also participants in the DISC...
  68. C/EBP-beta PEPTIDES FOR THE TREATMENT OF LIVER INJURY AND FIBROSIS
    Mario Chojkier; Fiscal Year: 2013
    ..C/EBP[unreadable]-Ala217 transgene prevents phosphorylation of endogenous C/EBP[unreadable], and activates caspase 8 resulting in apoptosis of HSC upon their activation, preventing progression and inducing regression liver ..
  69. Structural &Functional Studies of TLR/IL-1R Signaling
    Hao Wu; Fiscal Year: 2012
    ....
  70. HTS Screening for Inhibitors of HPV 16 E6/Caspase 8 Binding
    Penelope J Duerksen-Hughes; Fiscal Year: 2013
    ..The work described in this grant application is focused on finding molecules that could be turned into drugs that would be effective therapeutic treatments for HPV-associated cancers. ..
  71. BIOSYNTHESIS OF ENKEPHALIN OPIOID PEPTIDES
    Vivian Hook; Fiscal Year: 2009
    ..These findings will enhance our knowledge of the complexity of the endogenous opioid system. ..
  72. Morvarid Karimi; Fiscal Year: 2015
    ..Perlmutter, Mach and Schlaggar...
  73. 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. ..
  74. Protection of the cornea from UVB radiation by elevated potassium in tears
    John L Ubels; Fiscal Year: 2013
    ..The hypothesis will be tested that elevated [K+] will protect the superficial corneal cell layers from UV-induced apoptosis. ..