2019
FoxO transcription factors 1 regulate mouse preimplantation embryo development
Kuscu N, Gungor-Ordueri N, Sozen B, Adiguzel D, Celik-Ozenci C. FoxO transcription factors 1 regulate mouse preimplantation embryo development. Journal Of Assisted Reproduction And Genetics 2019, 36: 2121-2133. PMID: 31396850, PMCID: PMC6823425, DOI: 10.1007/s10815-019-01555-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBlastocystCell Cycle CheckpointsCell Cycle ProteinsEmbryonic DevelopmentFas Ligand ProteinFemaleForkhead Box Protein O1Forkhead Box Protein O3Forkhead Transcription FactorsGene Expression Regulation, DevelopmentalHumansMicep21-Activated KinasesPregnancySirtuin 1Tumor Suppressor Protein p53ConceptsPreimplantation embryo developmentFOXO transcription factorsFas ligandTranscription factorsRelated proteinsProteins regulating apoptosisPreimplantation embryosCell cycle related proteinsCleaved caspase 3 proteinsCell cycle arrestDevelopmental competence of embryosEmbryo developmentMouse preimplantation embryo developmentApoptosis-related proteinsMouse embryosCaspase 3 proteinTwo-cell mouse embryosResveratrol treatmentCompetence of embryosHuman preimplantation embryosMouse preimplantation embryosFOXO genesDUTP nick end labeling assayNick end labeling assayKnockdown embryosSMAC mimetics as potential cancer therapeutics in myeloid malignancies
Boddu P, Carter BZ, Verstovsek S, Pemmaraju N. SMAC mimetics as potential cancer therapeutics in myeloid malignancies. British Journal Of Haematology 2019, 185: 219-231. PMID: 30836448, DOI: 10.1111/bjh.15829.Peer-Reviewed Original ResearchConceptsSmac mimeticsSmall-molecule Smac mimeticsSecond mitochondria-derived activatorEvasion of apoptosisPro-apoptotic proteinsPotential cancer therapeuticsMyeloid malignanciesIAP antagonismApoptosis proteinIAP expressionApoptosis thresholdDeath receptorsCaspase proteinsCell deathImmune check-point blockadeIAP activityReceptor tyrosine kinase inhibitorsCheck-point blockadeCancer therapeuticsEffect of chemotherapyDirect targetingProteinTumor necrosis factorFas ligandTyrosine kinase inhibitors
2018
Fas Ligand localizes to intraluminal vesicles within NK cell cytolytic granules and is enriched at the immune synapse
Lee J, Dieckmann N, Edgar J, Griffiths G, Siegel R. Fas Ligand localizes to intraluminal vesicles within NK cell cytolytic granules and is enriched at the immune synapse. Immunity Inflammation And Disease 2018, 6: 312-321. PMID: 29642281, PMCID: PMC5946154, DOI: 10.1002/iid3.219.Peer-Reviewed Original ResearchConceptsIntraluminal vesiclesImmune synapseCytolytic granulesImmune synapsesCognate receptor FasType II transmembrane proteinFormation of immune synapsesMembrane-bound FasLNK cellsPerforin-containing granulesIntra-luminal vesiclesReceptor FasFusion proteinTransmembrane proteinsB cellsPlasma membraneFas ligandFasLImmunoelectron microscopyNK cell cytotoxicityHuman NK cellsFASDense-coreVesiclesPerforin/granzyme system
2009
Acidic Mammalian Chitinase Regulates Epithelial Cell Apoptosis via a Chitinolytic-Independent Mechanism
Hartl D, He CH, Koller B, Da Silva CA, Kobayashi Y, Lee CG, Flavell RA, Elias JA. Acidic Mammalian Chitinase Regulates Epithelial Cell Apoptosis via a Chitinolytic-Independent Mechanism. The Journal Of Immunology 2009, 182: 5098-5106. PMID: 19342690, PMCID: PMC2666938, DOI: 10.4049/jimmunol.0803446.Peer-Reviewed Original ResearchConceptsAcidic mammalian chitinaseTh2-mediated diseasesEpithelial cellsMammalian chitinasePI3K/Akt pathwayPulmonary epithelial cellsEpithelial cell apoptosisApoptosis-inhibiting effectsComparable cytoprotectionGrowth factor withdrawal-induced apoptosisChitinolytic activityEffector responsesParacrine mannerFas ligand-induced apoptosisAntiparasite responsesGrowth factor withdrawalWithdrawal-induced apoptosisLigand-induced apoptosisFas ligandAkt pathwayCell apoptosisAkt phosphorylationAMCaseBiologic propertiesCytoprotection
2008
The Placental Syncytium and the Pathophysiology of Preeclampsia and Intrauterine Growth Restriction
Guller S, Y. Y, Fu H, Krikun G, Abrahams VM, Mor G. The Placental Syncytium and the Pathophysiology of Preeclampsia and Intrauterine Growth Restriction. Annals Of The New York Academy Of Sciences 2008, 1127: 129-133. PMID: 18443340, PMCID: PMC3671376, DOI: 10.1196/annals.1434.015.Peer-Reviewed Original ResearchConceptsIntrauterine growth restrictionPathophysiology of preeclampsiaGrowth restrictionPlacental syncytiumFms-like tyrosine kinase-1Complications of pregnancyPlasminogen activator inhibitor-1Tyrosine kinase-1Activator inhibitor-1Release of factorsPlacental damageSoluble endoglinEndothelium dysfunctionLaser capture microdissectionMaternal bloodAntiangiogenic factorsPreeclampsiaFas ligandWestern blottingInhibitor-1Reactive oxygen speciesCapture microdissectionPregnancyPathophysiologyKinase 1
2007
IFN-γ and Fas Ligand Are Required for Graft-versus-Tumor Activity against Renal Cell Carcinoma in the Absence of Lethal Graft-versus-Host Disease
Ramirez-Montagut T, Chow A, Kochman A, Smith O, Suh D, Sindhi H, Lu S, Borsotti C, Grubin J, Patel N, Terwey T, Kim T, Heller G, Murphy G, Liu C, Alpdogan O, van den Brink M. IFN-γ and Fas Ligand Are Required for Graft-versus-Tumor Activity against Renal Cell Carcinoma in the Absence of Lethal Graft-versus-Host Disease. The Journal Of Immunology 2007, 179: 1669-1680. PMID: 17641033, DOI: 10.4049/jimmunol.179.3.1669.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaMurine renal cell carcinomaT cellsCell carcinomaGVT activityHost diseaseRenca cellsIFN-gammaTumor activityAllogeneic bone marrow transplantation modelFas ligandAbsence of graftRecipients of IFNBone marrow transplantation modelMechanism of graftMembrane-bound TNF-alphaTumor-bearing miceLethal graftLethal GVHDSevere GVHDTNF-alphaTransplantation modelTransplanted miceLytic capacitySolid tumors
2006
Sorting of Fas ligand to secretory lysosomes is regulated by mono-ubiquitylation and phosphorylation
Zuccato E, Blott E, Holt O, Sigismund S, Shaw M, Bossi G, Griffiths G. Sorting of Fas ligand to secretory lysosomes is regulated by mono-ubiquitylation and phosphorylation. Journal Of Cell Science 2006, 120: 191-199. PMID: 17164290, DOI: 10.1242/jcs.03315.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsEndosomesFas Ligand ProteinHeLa CellsHumansJurkat CellsLeukemia, Basophilic, AcuteLymphocyte Specific Protein Tyrosine Kinase p56(lck)LysosomesMolecular Sequence DataPhosphorylationProtein Structure, TertiaryProtein TransportProto-Oncogene ProteinsProto-Oncogene Proteins c-fynRatsSecretory VesiclesSignal Transductionsrc Homology Domainssrc-Family KinasesUbiquitinConceptsSecretory lysosomesMono-ubiquitylationMultivesicular bodiesProline-rich domainLyn tyrosine kinaseExosome-like vesiclesUbiquitin signalingCytoplasmic tailInner vesicleFas ligandPhosphorylationTyrosine kinaseFasLLysosomesControl entryFasL.LysineSortingUbiquitylationUbiquitinFynLynFASKinaseApoptosis
2004
Perforin and Fas Ligand Are Required for the Regulation of Alloreactive CD8+ T Cells.
Maeda Y, Levy R, Reddy P, Liu C, Teshima T, Ferrara J. Perforin and Fas Ligand Are Required for the Regulation of Alloreactive CD8+ T Cells. Blood 2004, 104: 3052. DOI: 10.1182/blood.v104.11.3052.3052.Peer-Reviewed Original ResearchDonor T cellsT cellsDonor CD8WT T cellsAlloreactive CD8Day 10Day 30Host antigen presenting cellsFas ligandSingle MHC class IHost dendritic cellsModel of graftT cell populationsAntigen presenting cellsT cell homeostasisFas ligand pathwayMHC class IAllogeneic CD8Bm1 miceLethal GVHDSevere GVHDSignificant GVHDHost diseaseBMT recipientsEpithelial target cellsRegulation of Fas ligand expression by vascular endothelial growth factor in endometrial stromal cells in vitro
Berkkanoglu M, Guzeloglu-Kayisli O, Kayisli U, Selam B, Arici A. Regulation of Fas ligand expression by vascular endothelial growth factor in endometrial stromal cells in vitro. Molecular Human Reproduction 2004, 10: 393-398. PMID: 15073283, DOI: 10.1093/molehr/gah060.Peer-Reviewed Original ResearchConceptsStromal cell survivalCell survivalStromal cellsVascular endothelial growth factorEndometrial stromal cellsPotent mitogenic cytokineFasL expressionGrowth factorRegulation of FasLApoptotic signalingTranslation levelsFas ligand expressionWestern blot analysisEndothelial growth factorFas receptorFasL levelsBlot analysisFas ligandExpression of FasLConcentration-dependent mannerMitogenic cytokinesEffects of VEGFRegulationExpressionParacrine mannerA Novel Immortalized Human Endometrial Stromal Cell Line with Normal Progestational Response
Krikun G, Mor G, Alvero A, Guller S, Schatz F, Sapi E, Rahman M, Caze R, Qumsiyeh M, Lockwood CJ. A Novel Immortalized Human Endometrial Stromal Cell Line with Normal Progestational Response. Endocrinology 2004, 145: 2291-2296. PMID: 14726435, DOI: 10.1210/en.2003-1606.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TransformedDeciduaEndometriumEstradiolFas Ligand Proteinfas ReceptorFemaleFibronectinsGene ExpressionHot TemperatureHumansInsulin-Like Growth Factor Binding Protein 1KaryotypingMedroxyprogesterone AcetateMembrane GlycoproteinsPlasminogen Activator Inhibitor 1ProgestinsProlactinStromal CellsTelomeraseThromboplastinConceptsHuman endometrial stromal cellsImmortalized human endometrial stromal cell lineHuman endometrial stromal cell lineCultured human endometrial stromal cellsEndometrial stromal cell linePrimary human endometrial stromal cellsPlasminogen activator inhibitor-1Endometrial stromal cellsExpression of IGFFas/Fas ligandActivator inhibitor-1Cell linesProgestational responseParent cellsOvarian steroidsMedroxyprogesterone acetateDecidualization responseAbnormal karyotypeStromal cell lineTissue factorNew cell lineStromal cellsFas ligandInhibitor-1Process of immortalizationFirst trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis
Abrahams VM, Straszewski-Chavez S, Guller S, Mor G. First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Molecular Human Reproduction 2004, 10: 55-63. PMID: 14665707, DOI: 10.1093/molehr/gah006.Peer-Reviewed Original ResearchConceptsFirst trimester trophoblast cellsImmune privilegeTrophoblast cellsFas/Fas ligand (FasL) apoptotic pathwayMaternal immune recognitionMaternal immune systemImmune cell apoptosisSecretion of FasLT cell deathPaternal alloantigensAllograft rejectionNormal pregnancyPeripheral toleranceImmune recognitionImmune systemRelease of microvesiclesFas ligandCell apoptosisVivo studiesFasLMembrane-associated expressionTrophoblastIntracellular FasLApoptotic pathwayDeath
2003
Lytic granules, secretory lysosomes and disease
Clark R, Griffiths G. Lytic granules, secretory lysosomes and disease. Current Opinion In Immunology 2003, 15: 516-521. PMID: 14499259, DOI: 10.1016/s0952-7915(03)00113-4.Peer-Reviewed Original ResearchConceptsSecretory lysosomesLytic granulesLysosomal functionApoptosis-inducing moleculesHermansky-Pudlak syndromeLysosomal secretionFas ligandGenetic diseasesLysosomesExcellent modelProteinLytic componentHemopoietic cellsCellsImmune systemFASMelanocytesHaemopoietic cellsGranulesNatural killer cellsGeneticsKiller cellsFunction of cytotoxic T lymphocytesApoptosis and the Pathogenesis of Endometriosis
Garcia-Velasco J, Arici A. Apoptosis and the Pathogenesis of Endometriosis. Seminars In Reproductive Medicine 2003, 21: 165-172. PMID: 12917786, DOI: 10.1055/s-2003-41323.Peer-Reviewed Original ResearchConceptsPathogenesis of endometriosisEndometrial cellsSex steroid modulationDisease-free womenEutopic endometrial cellsBcl-2/BaxEndometriotic implantsSteroid modulationInflammatory environmentInflammatory reactionAbnormal survivalEndometriosisApoptosis-related genesFas ligandPhysiologic processesEarly eventsPathogenesisApoptosis
2002
Porcine Endothelial Cells, Unlike Human Endothelial Cells, Can Be Killed by Human CTL Via Fas Ligand and Cannot Be Protected by Bcl-2
Zheng L, Ben LH, Pober JS, Bothwell AL. Porcine Endothelial Cells, Unlike Human Endothelial Cells, Can Be Killed by Human CTL Via Fas Ligand and Cannot Be Protected by Bcl-2. The Journal Of Immunology 2002, 169: 6850-6855. PMID: 12471117, DOI: 10.4049/jimmunol.169.12.6850.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, HeterophileApoptosisCD8-Positive T-LymphocytesCell LineCell Line, TransformedCoculture TechniquesCytotoxicity Tests, ImmunologicCytotoxicity, ImmunologicEndothelium, VascularEpitopes, T-LymphocyteFas Ligand Proteinfas ReceptorGenetic VectorsGranzymesHistocompatibility Antigens Class IHumansImmunity, InnateIsoantigensLigandsMembrane GlycoproteinsPerforinPore Forming Cytotoxic ProteinsProto-Oncogene Proteins c-bcl-2Serine EndopeptidasesSwineT-Lymphocytes, CytotoxicConceptsHuman endothelial cellsPorcine endothelial cellsEndothelial cellsBcl-2MHC class I restrictionClass I restrictionPorcine aortic endothelial cellsTarget cell recognitionAnti-Fas ligand AbAortic endothelial cellsHost CTLAcute rejectionCTL responsesDrug-induced apoptosisHuman CTLPorcine targetsTarget cell typeHuman xenotransplantationFAS expressionFas ligandPorcine cellsCTLMajor effectorCell recognitionMajor target
2001
Fas ligand is targeted to secretory lysosomes via a proline-rich domain in its cytoplasmic tail
Blott E, Bossi G, Clark R, Zvelebil M, Griffiths G. Fas ligand is targeted to secretory lysosomes via a proline-rich domain in its cytoplasmic tail. Journal Of Cell Science 2001, 114: 2405-2416. PMID: 11559749, DOI: 10.1242/jcs.114.13.2405.Peer-Reviewed Original ResearchConceptsProline-rich domainSecretory lysosomesPlasma membraneCytoplasmic tailSH3 domain-containing proteinsCell surface receptor FasFas ligandCell surface expression of FasLSH3-domain-containingSurface expression of FasLCell typesPositively charged residuesMis-sortingSorting motifDeletion mutantsExpression of FasLReceptor FasEndogenous FasLInduce apoptosisCharged residuesCell surface expressionLysosomal compartmentFasLLysosomesMotifAtm knock-in mice harboring an in-frame deletion corresponding to the human ATM 7636del9 common mutation exhibit a variant phenotype.
Spring K, Cross S, Li C, Watters D, Ben-Senior L, Waring P, Ahangari F, Lu SL, Chen P, Misko I, Paterson C, Kay G, Smorodinsky NI, Shiloh Y, Lavin MF. Atm knock-in mice harboring an in-frame deletion corresponding to the human ATM 7636del9 common mutation exhibit a variant phenotype. Cancer Research 2001, 61: 4561-8. PMID: 11389091.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAtaxia TelangiectasiaAtaxia Telangiectasia Mutated ProteinsBase SequenceCell Cycle ProteinsCrosses, GeneticDNADNA-Binding ProteinsFemaleHumansLymphomaMaleMiceMice, Inbred C57BLMice, KnockoutMice, Mutant StrainsMutagenesis, Site-DirectedPhenotypeProtein Serine-Threonine KinasesSequence DeletionThymus NeoplasmsTumor Suppressor ProteinsUp-RegulationConceptsAtaxia telangiectasiaFrame deletionDisorder ataxia-telangiectasiaProtein kinase activityCell cycle checkpointsAmino acid residuesSelectable marker cassetteDetectable ATM proteinMutant proteinsATM proteinCycle checkpointsHomologous recombinationKinase activityAcid residuesMarker cassetteCommon deletion mutationsDeletion mutationsDeletion resultsCre-loxPATM geneThymic lymphomasExtensive apoptosisVariant phenotypesDifferent phenotypesFas ligand
2000
Roles of Fas and Fas ligand during mammary gland remodeling
Song J, Sapi E, Brown W, Nilsen J, Tartaro K, Kacinski B, Craft J, Naftolin F, Mor G. Roles of Fas and Fas ligand during mammary gland remodeling. Journal Of Clinical Investigation 2000, 106: 1209-1220. PMID: 11086022, PMCID: PMC381435, DOI: 10.1172/jci10411.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBlotting, WesternCaspase 3CaspasesCell LineCulture MediaCulture Media, Serum-FreeDexamethasoneEpithelial CellsFas Ligand Proteinfas ReceptorFemaleGene ExpressionHumansMammary Glands, AnimalMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C3HMice, Inbred MRL lprMice, KnockoutPregnancyPregnancy, AnimalRNA, MessengerConceptsMammary epithelial cellsFas/FasL signalsMouse mammary epithelial cellsMammary gland remodelingFasL proteinApoptotic cellsEpithelial cellsInduction of apoptosisAccumulation of cellsSubsequent neoplastic developmentRole of FasMammary gland tissueFasL signalsMammary tissueCell deathExpression of FasFas-FasL interactionMouse mammary tissueMammary cellsCaspase-3Autocrine inductionFas ligandMammary epitheliumNeoplastic developmentTumor developmentSorting out the multiple roles of Fas ligand
Bossi G, Stinchcombe J, Page L, Griffiths G. Sorting out the multiple roles of Fas ligand. European Journal Of Cell Biology 2000, 79: 539-543. PMID: 11001490, DOI: 10.1078/0171-9335-00077.Peer-Reviewed Original Research
1999
Degranulation plays an essential part in regulating cell surface expression of Fas ligand in T cells and natural killer cells
Bossi G, Griffiths G. Degranulation plays an essential part in regulating cell surface expression of Fas ligand in T cells and natural killer cells. Nature Medicine 1999, 5: 90-96. PMID: 9883845, DOI: 10.1038/4779.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteCathepsin DCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DegranulationCell FractionationCell LineFas Ligand ProteinGene ExpressionGranzymesHeLa CellsHumansKiller Cells, NaturalLectins, C-TypeLysosomesMembrane GlycoproteinsMicePerforinPlatelet Membrane GlycoproteinsPore Forming Cytotoxic ProteinsRatsSerine EndopeptidasesTetraspanin 30ConceptsSecretory lysosomesTrigger apoptosisFas ligandSpecialized secretory lysosomesCell surface expressionCell surface expression of FasLCell surfaceSurface expression of FasLFasL-mediated apoptosisRegulating cell surface expressionCell surface appearanceNatural killer cellsExpression of FasLAppearance of proteinsCytoplasmic tailFasLFasL expressionKiller cellsT cellsApoptosisPolarized degranulationTarget-cell recognitionFASLysosomesCD8+ T cells
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