Genomes and Genes
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
Publications302 found, 100 shown here
- CASH, a novel caspase homologue with death effector domainsY 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...
- Rapid cytochrome c release, activation of caspases 3, 6, 7 and 8 followed by Bap31 cleavage in HeLa cells treated with photodynamic therapyD 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...
- Caspase-10 is an initiator caspase in death receptor signalingJ 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...
- The structure of FADD and its mode of interaction with procaspase-8Paul 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...
- Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammationYoung 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...
- The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPsTencho 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...
- Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a noncanonical caspase-8 inflammasomeSonja 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...
- Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaBN 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...
- Stoichiometry of the CD95 death-inducing signaling complex: experimental and modeling evidence for a death effector domain chain modelKolja 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...
- Human immunodeficiency virus type 1 Vpr induces apoptosis in human neuronal cellsC 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...
- Caspase-8 cleaves its substrates from the plasma membrane upon CD95-induced apoptosisJ 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...
- Genetic polymorphisms of the CASP8 gene promoter may not be associated with colorectal cancer in Han Chinese from southwest ChinaMei 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. 2013b>Caspase 8 (CASP8) plays a critical role in the apoptotic pathway and aberrant regulation of this pathway causes many diseases including cancers...
- Functions of Tat: the versatile protein of human immunodeficiency virus type 1Bizhan 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...
- HIV-1 viral protein r induces ERK and caspase-8-dependent apoptosis in renal tubular epithelial cellsAlexandra 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...
- Following cytochrome c release, autophagy is inhibited during chemotherapy-induced apoptosis by caspase 8-mediated cleavage of Beclin 1Hua 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...
- TWEAK induces apoptosis through a death-signaling complex comprising receptor-interacting protein 1 (RIP1), Fas-associated death domain (FADD), and caspase-8Aminah 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...
- Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosisY 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...
- Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1Jean 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...
- Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell deathA 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 ..
- Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cellsChangjiang 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...
- RNA silencing of Mcl-1 enhances ABT-737-mediated apoptosis in melanoma: role for a caspase-8-dependent pathwayAngela 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...
- Caspase 8 inhibits programmed necrosis by processing CYLDMarie Anne O'Donnell
Immunology Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
Nat Cell Biol 13:1437-42. 2011b>Caspase 8 initiates apoptosis downstream of TNF death receptors by undergoing autocleavage and processing the executioner caspase 3 (ref. 1)...
- Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner HippiFrancois 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...
- Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector moleculeN 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...
- Polymorphisms of caspase 8 and caspase 9 gene and colorectal cancer susceptibility and prognosisGeorge 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...
- ABIN-1 is a ubiquitin sensor that restricts cell death and sustains embryonic developmentShigeru 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, ..
- Virion-associated Vpr of human immunodeficiency virus type 1 triggers activation of apoptotic events and enhances fas-induced apoptosis in human T cellsHubert 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...
- The caspase-8 dimerization/dissociation balance is a highly potent regulator of caspase-8, -3, -6 signalingMaximilian 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...
- FLASH links the CD95 signaling pathway to the cell nucleus and nuclear bodiesKristijana Milovic-Holm
Heinrich Pette Institut für Experimentelle Virologie und Immunologie, Hamburg, Germany
EMBO J 26:391-401. 2007Caspase-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...
- 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 mechanismZhan 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 ..
- Caspase-1 and caspase-8 cleave and inactivate cellular parkinSoren Kahns
Department of Molecular Biology, University of Aarhus, DK 8000 Aarhus C, Denmark
J Biol Chem 278:23376-80. 2003....
- Characterization of caspase-8L: a novel isoform of caspase-8 that behaves as an inhibitor of the caspase cascadeDaisuke Himeji
Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Japan
Blood 99:4070-8. 2002Caspase-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...
- Expression of short-form caspase 8 correlates with decreased sensitivity to Fas-mediated apoptosis in neuroblastoma cellsRodrick 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...
- Caspase-8 gene expression in neuroblastomaIda 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...
- Palmitoylation of CD95 facilitates formation of SDS-stable receptor aggregates that initiate apoptosis signalingChristine 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...
- Caspase 9 and caspase 8 gene polymorphisms and susceptibility to bladder cancer in north Indian populationRuchika 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. 2009Dysregulation 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.
- CASP8 -652 6N del polymorphism and cancer risk: a meta-analysis of 30 case-control studies in 50,112 subjectsFan 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...
- Dominant expression of a novel splice variant of caspase-8 in human peripheral blood lymphocytesT 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...
- The CASP8 -652 6N insertion/deletion promoter polymorphism is associated with renal cell carcinoma risk and metastasisMichela 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...
- Polymorphisms in the promoter region of the CASP8 gene are not associated with non-Hodgkin's lymphoma in Chinese patientsMei 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...
- Recruitment of TNF receptor 1 to lipid rafts is essential for TNFalpha-mediated NF-kappaB activationDaniel 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...
- Association of polymorphisms in CASP10 and CASP8 with FEV(1)/FVC and bronchial hyperresponsiveness in ethnically diverse asthmaticsAlicia 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...
- Glucocorticoid-induced activation of caspase-8 protects the glucocorticoid-induced protein Gilz from proteasomal degradation and induces its binding to SUMO-1 in murine thymocytesD 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...
- 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 techniquesYing 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....
- 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 individualsStacey 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...
- Inhibition of protein degradation induces apoptosis through a microtubule-associated protein 1 light chain 3-mediated activation of caspase-8 at intracellular membranesJi 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...
- Smad7 protein induces interferon regulatory factor 1-dependent transcriptional activation of caspase 8 to restore tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosisSuntaek 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...
- IL-6 cytoprotection in hyperoxic acute lung injury occurs via suppressor of cytokine signaling-1-induced apoptosis signal-regulating kinase-1 degradationNarasaiah 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...
- Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibitionSai 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...
- 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-8Martin 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...
- Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomainV 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...
- Cardiolipin provides an essential activating platform for caspase-8 on mitochondriaFrancois Gonzalvez
Cancer Research UK, The Beatson Institute for Cancer Research, Glasgow, Scotland, UK
J Cell Biol 183:681-96. 2008....
- Inducible dimerization and inducible cleavage reveal a requirement for both processes in caspase-8 activationAndrew Oberst
Department of Immunology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
J Biol Chem 285:16632-42. 2010....
- The CASP8 -652 6N del promoter polymorphism and breast cancer risk: a multicenter studyBernd 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...
- HIV-1 protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload, and oxidative stressI 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...
- 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-1Carmen 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...
- 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 cellsMoon 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...
- 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 complexShyam 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...
- A CASP-8 mutation recognized by cytolytic T lymphocytes on a human head and neck carcinomaS 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 ..
- Identification of the cytolinker plectin as a major early in vivo substrate for caspase 8 during CD95- and tumor necrosis factor receptor-mediated apoptosisA H Stegh
Tumor Immunology Program, German Cancer Research Center, D 69120 Heidelberg, Germany
Mol Cell Biol 20:5665-79. 2000b>Caspase 8 plays an essential role in the execution of death receptor-mediated apoptosis...
- CASP8 polymorphisms contribute to cancer susceptibility: evidence from a meta-analysis of 23 publications with 55 individual studiesMing Yin
Department of Epidemiology, The University of Texas, M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Carcinogenesis 31:850-7. 2010Several potentially functional polymorphisms of CASP8 encoding an apoptotic enzyme, caspase 8, have been implicated in cancer risk, but individually published studies showed inconclusive results...
- CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzymeT 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...
- Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activationY 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...
- Human immunodeficiency virus type 1 Tat induces apoptosis and increases sensitivity to apoptotic signals by up-regulating FLICE/caspase-8S 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...
- HIV-1 Vpr induces apoptosis through caspase 9 in T cells and peripheral blood mononuclear cellsKaruppiah 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 ..
- Interferon-gamma differentially regulates monocyte matrix metalloproteinase-1 and -9 through tumor necrosis factor-alpha and caspase 8Min 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...
- The Siva protein is a novel intracellular ligand of the CD4 receptor that promotes HIV-1 envelope-induced apoptosis in T-lymphoid cellsBénédicte 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...
- Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiencyHyung 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...
- Caspase-8 interacts with the p85 subunit of phosphatidylinositol 3-kinase to regulate cell adhesion and motilityJamie 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...
- Association of the CASP10 V410I variant with reduced familial breast cancer risk and interaction with the CASP8 D302H variantBernd 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...
- Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell deathM 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...
- FLICE induced apoptosis in a cell-free system. Cleavage of caspase zymogensM 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...
- Activation of the NF-kappaB pathway by caspase 8 and its homologsP M Chaudhary
Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, Texas, TX 75390 8593, USA
Oncogene 19:4451-60. 2000b>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...
- Differential inactivation of caspase-8 in lung cancersNarayan 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...
- Silencing of death receptor and caspase-8 expression in small cell lung carcinoma cell lines and tumors by DNA methylationS 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...
- Amplification of CD95 activation by caspase 8-induced endosomal acidification in rat hepatocytesRoland 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(-)], ..
- Mutational analysis of CASP1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 14 genes in gastrointestinal stromal tumorsYoo Ri Kim
Department of Pathology, The Catholic University of Korea, Seoul, Korea
Hum Pathol 40:868-71. 2009....
- Casper is a FADD- and caspase-related inducer of apoptosisH 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...
- p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulumF 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)...
- Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosisH 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...
- Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha-induced apoptosisD 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...
- Inactivation of caspase-8 on mitochondria of Bcl-xL-expressing MCF7-Fas cells: role for the bifunctional apoptosis regulator proteinAlexander H Stegh
Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 277:4351-60. 2002....
- The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at the endoplasmic reticulumDavid 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...
- TRAIL receptor and CD95 signal to mitochondria via FADD, caspase-8/10, Bid, and Bax but differentially regulate events downstream from truncated BidArlette 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...
- A unified model for apical caspase activationKelly 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...
- Paclitaxel-induced apoptosis in BJAB cells proceeds via a death receptor-independent, caspases-3/-8-driven mitochondrial amplification loopClarissa 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...
- Fas-associated factor 1, FAF1, is a member of Fas death-inducing signaling complexSeung 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...
- 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 apoptosisNicholas 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....
- The human caspase-8 promoter sustains basal activity through SP1 and ETS-like transcription factors and can be up-regulated by a p53-dependent mechanismChristian Liedtke
Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover, D 30625 Hannover, Germany
J Biol Chem 278:27593-604. 2003Caspase-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 ..
- Caspase 8-mediated cleavage of the pro-apoptotic BCL-2 family member BID in p53-dependent apoptosisBarbara 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 ..
- Interdimer processing mechanism of procaspase-8 activationDavid 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...
- 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 deathDhyan 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...
- A common coding variant in CASP8 is associated with breast cancer riskAngela 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...
- A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is associated with susceptibility to multiple cancersTong 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...
- Novel noncatalytic role for caspase-8 in promoting SRC-mediated adhesion and Erk signaling in neuroblastoma cellsDarren 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...
- Mutation of a self-processing site in caspase-8 compromises its apoptotic but not its nonapoptotic functions in bacterial artificial chromosome-transgenic miceTae Bong Kang
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
J Immunol 181:2522-32. 2008....
- Clinicopathological significance of caspase-8 and caspase-10 expression in rectal cancerBing 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...
- Caspase 8 promotes peripheral localization and activation of Rab5Vicente 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. 2008b>Caspase 8 is a cysteine protease that initiates apoptotic signaling via the extrinsic pathway in a manner dependent upon association with early endosomes...
- Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a pooled analysis of 3 population-based case-control studiesQing 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...
- Critical role for caspase-8 in epidermal growth factor signalingDarren 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...
- Association of selected polymorphisms of CCND1, p21, and caspase8 with colorectal cancer riskBing 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...
- Caspases, Calpains and Neuronal Cell deathStan 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. ..
- Programmed necrosis in Immune ResponsesFrancis 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...
- HOW ENVIRONMENTAL CHEMICALS IMPAIR IMMUNITYDavid Sherr; Fiscal Year: 2009....
- Engineering tyrosine kinase-activated caspases for selective cancer cell killingSALLY 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 ..
- NIH Director's Pioneer AwardJunying Yuan; Fiscal Year: 2009..No Abstract provided ..
- C/EBP beta SIGNALS HEPATOCYTE PROLIFERATION AND SURVIVALMario 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...
- HTS for Caspase-8 selective TRAIL SensitizersKristiina 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. ..
- Guy S Salvesen; Fiscal Year: 2015....
- Douglas R Green; Fiscal Year: 2016....
- 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 ..
- 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. ..
- Novel Fas/CD95 Signaling MechanismsMarcus 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. ..
- EOSINOPHIL APOPTOSIS IN ASTHMAGerald Litwack; Fiscal Year: 2001..Furthermore, manipulation of these pathways will be a key area for therapeutic intervention in asthma. ..
- Non-apoptotic functions of caspasesSTEVEN 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. ..
- Cathepsin L in the Biosynthesis of Enkephalins and beta-Endorphin Opioid PeptidesSteven J Bark; Fiscal Year: 2012....
- 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. ..
- Stephen J Davies; Fiscal Year: 2014....
- Dietmar W Siemann; Fiscal Year: 2016....
- Telomerase Specific Caspase Transfer for GliomasSeiji 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. ..
- The Role of Caspase-8 in Alzheimer's DiseaseTroy Rohn; Fiscal Year: 2001....
- 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. ..
- Ethan A Lerner; Fiscal Year: 2014..The results of this project may lead to the development of new drugs to treat itch. ..
- Controlled expression of a cystatin C-peptide as therapy for Alzheimer's diseasePHYLLIS ANN SHAW; Fiscal Year: 2012....
- CYSTEINE PROTEASES & INHIBITORS IN NEMATODE DEVELOPMENTSara Lustigman; Fiscal Year: 2000..This will provide the basis for developing effective drugs targeting cysteine protease to control onchocerciasis and filariasis in the future. ..
- 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. ..
- Development of protease inhibitor drugs to treat Alzheimer's diseaseGREGORY 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. ..
- 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. ..
- Fic-mediated AdenylylationCAROLYN ANN WORBY; Fiscal Year: 2013..This covalent addition of AMP blocks signal transduction pathways in the host that are important for combating bacterial infections. ..
- 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. ..
- Molecular mechanisms of pathogen recognition by the Nod-like receptor NLRC4Fayyaz S Sutterwala; Fiscal Year: 2012..iii) Determining if NLRC4 recognizes host plasma membrane components following their disruption by bacterial T3SS. ..
- K777 for treatment of Chagas Disease: IND-enabling Studies and IND SubmissionRobert 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. ..
- 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. ..
- 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. ..
- Richard C Condit; Fiscal Year: 2014....
- Role of HCV p7 and NS2 in infectious virus productionCharles M Rice; Fiscal Year: 2012..The resulting findings should aid development of more effective treatments aimed at eradicating this deadly viral disease. ..
- Vishwa Deep Dixit; Fiscal Year: 2014....
- 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. ..
- Characterization of a novel protein required for glomerular podocyte functionLORI 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. ..
- Imaging of Cardiac Transplant RejectionMatthias Nahrendorf; Fiscal Year: 2013..These longitudinal studies will be used to validate functional macrophage-targeted agents for noninvasive heart transplant imaging. ..
- 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. ..
- Functional characterization of Rho inactivation by Vibro cholerae RTX toxinBRETT 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. ..
- Genetic and Biochemical Study of V. cholerae RTX ToxinKarla 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. ..
- Repression of inflammasome by Francisella tularensisMeenakshi Malik; Fiscal Year: 2013..This proposal is a step ahead in understanding the immunopathogenesis of tularemia. ..
- Timothy Tellinghuisen; Fiscal Year: 2014....
- Chemically Interrogating Clostridium difficile Glucosylating Toxin ActivationAimee 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. ..
- Mechanism and Inhibition of Arginine DeiminaseHua 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. ..
- 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. ..
- Cytomegalovirus Deubiquitinase pUL48: Identifying Substrate and InhibitorsD 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. ..
- Al-2-Dependent Quorum Sensing in the Gram-Positive Bacterium Streptococcus pyogenMichael 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. ..
- Dysregulation of ubiquitination in MALT lymphomasXiaolu Yang; Fiscal Year: 2010....
- Neural Mechanisms of ItchROBERT H LA MOTTE; Fiscal Year: 2013..abstract_text> ..
- Chemically Interrogating Clostridium difficile Glucosylating Toxin ActivationAimee 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. ..
- 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. ..
- 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. ..
- Role of Red Cell Membrane in Malaria Parasite ReleaseManjit 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. ..
- Identifying Calpain-10 Substrates from Human ProteomeRihe Liu; Fiscal Year: 2005..abstract_text> ..
- Promiscuous and Specific Inhibitors of CruzainBrian 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]..
- Role of cysteine proteases in malaria transmissionKIM 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. ..
- MAST CELL CYSTEINE PROTEASES IN LUNG INFLAMMATIONPaul 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. ..
- BIOLOGICAL Function of the Retinoblastoma Gene ProductJean 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. ..
- 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...
- Pro-apoptotic BID in DNA Damage and LeukemogenesisSandra S Zinkel; Fiscal Year: 2011..Cleavage by caspase 8 and myristoylation serve to activate BID, facilitating targeting to the mitochondria where it activates ..
- Apoptosis and Trophoblast FusionNEAL STEWART ROTE; Fiscal Year: 2010..that villous cytotrophoblast fusion results from aborted activation of apoptotic pathways, particularly through caspase 8-mediated PS efflux...
- 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. ..
- The Role of Caspase-8 in Neuroblastoma TumorigenesisGERARD 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. ..
- Dwayne G Stupack; Fiscal Year: 2014b>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 ..
- 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...
- C/EBP-beta PEPTIDES FOR THE TREATMENT OF LIVER INJURY AND FIBROSISMario 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 ..
- Structural &Functional Studies of TLR/IL-1R SignalingHao Wu; Fiscal Year: 2012....
- HTS Screening for Inhibitors of HPV 16 E6/Caspase 8 BindingPenelope 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. ..
- BIOSYNTHESIS OF ENKEPHALIN OPIOID PEPTIDESVivian Hook; Fiscal Year: 2009..These findings will enhance our knowledge of the complexity of the endogenous opioid system. ..
- Morvarid Karimi; Fiscal Year: 2015..Perlmutter, Mach and Schlaggar...
- CYSTEINE PROTEASES & INHIBITORS IN NEMATODE DEVELOPMENTSara Lustigman; Fiscal Year: 2005..This will provide the basis for developing effective drugs, targeting cysteine proteases, to control onchocerciasis and filariasis in the future. ..
- Protection of the cornea from UVB radiation by elevated potassium in tearsJohn L Ubels; Fiscal Year: 2013..The hypothesis will be tested that elevated [K+] will protect the superficial corneal cell layers from UV-induced apoptosis. ..