2019
TIGIT signaling restores suppressor function of Th1 Tregs
Lucca LE, Axisa PP, Singer ER, Nolan NM, Dominguez-Villar M, Hafler DA. TIGIT signaling restores suppressor function of Th1 Tregs. JCI Insight 2019, 4: e124427. PMID: 30728325, PMCID: PMC6413794, DOI: 10.1172/jci.insight.124427.Peer-Reviewed Original ResearchIL-12Multiple sclerosisHuman autoimmune disordersT-bet expressionProinflammatory cytokine secretionProduction of IFNType 1 diabetesReduced suppressor activitySuppressor functionRepression of AktFOXO1 nuclear localizationTh1 programTIGIT pathwayCoinhibitory receptorsImmunomodulatory therapyTh17 responsesAutoimmune disordersAutoimmune diseasesSuppressor defectCytokine secretionTregsTIGITProtective effectFunctional inhibitionAkt pathway
2018
Loss of KDM6A Activates Super-Enhancers to Induce Gender-Specific Squamous-like Pancreatic Cancer and Confers Sensitivity to BET Inhibitors
Andricovich J, Perkail S, Kai Y, Casasanta N, Peng W, Tzatsos A. Loss of KDM6A Activates Super-Enhancers to Induce Gender-Specific Squamous-like Pancreatic Cancer and Confers Sensitivity to BET Inhibitors. Cancer Cell 2018, 33: 512-526.e8. PMID: 29533787, PMCID: PMC5854186, DOI: 10.1016/j.ccell.2018.02.003.Peer-Reviewed Original ResearchConceptsPancreatic cancerCOMPASS-like complexesBET inhibitorsMetastatic pancreatic cancerSensitivity to BET inhibitorsSubtypes of tumorsSpectrum of malignanciesPatient-tailored therapySuper-enhancersActivation of super-enhancersSquamous-likeTumor suppressor functionSquamous differentiationRestrained tumor growthTailored therapyTumor growthTherapeutic nicheKDM6A lossSuppressor functionAberrant activationKDM6ACancerCharacterized mechanismsInhibitorsConcomitant loss
2017
Membrane‐bound Dickkopf‐1 in Foxp3+ regulatory T cells suppresses T‐cell‐mediated autoimmune colitis
Chae W, Park J, Henegariu O, Yilmaz S, Hao L, Bothwell ALM. Membrane‐bound Dickkopf‐1 in Foxp3+ regulatory T cells suppresses T‐cell‐mediated autoimmune colitis. Immunology 2017, 152: 265-275. PMID: 28556921, PMCID: PMC5588763, DOI: 10.1111/imm.12766.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAutoimmune DiseasesAutoimmunityCell MembraneCell ProliferationCHO CellsColitisColonCricetulusDisease Models, AnimalDNA-Binding ProteinsForkhead Transcription FactorsGenetic Predisposition to DiseaseIntercellular Signaling Peptides and ProteinsLymphocyte ActivationMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein KinasesPhenotypeSelf ToleranceSignal TransductionT-Lymphocytes, RegulatoryTime FactorsTransfectionConceptsRegulatory T cellsTreg cellsDKK-1 expressionAutoimmune colitisDickkopf-1T cellsT cell-mediated toleranceEffector CD4 T cellsCD4 T cellsInduction of toleranceT cell proliferationT cell receptor stimulationNovel TregColitis modelImmunological homeostasisImmunological toleranceFoxp3Receptor stimulationCanonical Wnt pathwayColitisFunctional inhibitionMonoclonal antibodiesDe novo protein synthesisProtein kinase pathwaySuppressor functionGenetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre–B ALL
Schjerven H, Ayongaba EF, Aghajanirefah A, McLaughlin J, Cheng D, Geng H, Boyd JR, Eggesbø LM, Lindeman I, Heath JL, Park E, Witte ON, Smale ST, Frietze S, Müschen M. Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre–B ALL. Journal Of Experimental Medicine 2017, 214: 793-814. PMID: 28190001, PMCID: PMC5339667, DOI: 10.1084/jem.20160049.Peer-Reviewed Original ResearchConceptsTumor suppressor functionHuman BCR-ABL1Target genesSuppressor functionDevelopmental stage-specific expressionGenome-wide chromatinStage-specific expressionWild-type IkarosTumor suppressor geneChromatin compactionIkaros functionGene pathwaysMultiple genesExpression analysisGenetic analysisInducible expressionTumor suppressorGenetic depletionCell surface markers CD34Suppressor geneGenesIkarosBCR-ABL1Cell acute lymphoblastic leukemiaLeukemic growth
2016
AKT isoforms modulate Th1‐like Treg generation and function in human autoimmune disease
Kitz A, de Marcken M, Gautron AS, Mitrovic M, Hafler DA, Dominguez-Villar M. AKT isoforms modulate Th1‐like Treg generation and function in human autoimmune disease. EMBO Reports 2016, 17: 1169-1183. PMID: 27312110, PMCID: PMC4967959, DOI: 10.15252/embr.201541905.Peer-Reviewed Original ResearchMeSH KeywordsAutoimmune DiseasesBiomarkersCell DifferentiationCytokinesForkhead Transcription FactorsGene Expression ProfilingGene SilencingHumansImmunomodulationInterferon-gammaPhenotypePhosphatidylinositol 3-KinasesProtein IsoformsProto-Oncogene Proteins c-aktSignal TransductionT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryTranscriptomeConceptsAutoimmune diseasesIFNγ secretionHuman TregsGenome-wide gene expression approachUntreated relapsing-remitting MS patientsRelapsing-remitting MS patientsImmune suppressive functionHuman autoimmune diseasesT helper 1Inflammatory cytokines IFNγTreg suppressor functionNovel treatment paradigmEffector phenotypeMS patientsTreg generationCytokines IFNγHelper 1Multiple sclerosisTreatment paradigmSuppressive functionTregsVivo modelDiseaseSecretionSuppressor functionKinase-Dependent and -Independent Roles for PTK6 in Colon Cancer
Mathur PS, Gierut JJ, Guzman G, Xie H, Xicola RM, Llor X, Chastkofsky MI, Perekatt AO, Tyner AL. Kinase-Dependent and -Independent Roles for PTK6 in Colon Cancer. Molecular Cancer Research 2016, 14: 563-573. PMID: 26983689, PMCID: PMC4912439, DOI: 10.1158/1541-7786.mcr-15-0450.Peer-Reviewed Original ResearchConceptsContext-specific functionsKinase-independent mannerEpithelial-mesenchymal transitionOncogenic signalingEpithelial phenotypeXenograft tumor growthCell survivalExpression of PTK6Protein tyrosine kinase 6DNA-damaging treatmentsTumor suppressor functionTyrosine kinase 6Colon cancer cellsDifferentiated epithelial cellsPTK6 knockdownTumor tissue arraysColon tumor cell linesHuman colon tumor cell linesPTK6 expressionKinase 6ERK5 activationPTK6Tumor growthDNA damageSuppressor functionAnalysis of Ikaros tumor suppressor function in BCR-ABL1+ pre-B ALL reveals conserved target genes and biological pathways
Schjerven H, Ayongaba E, McLaughlin J, Cheng D, Eggesbø L, Lindeman I, Park E, Witte O, Smale S, Frietze S, Muschen M. Analysis of Ikaros tumor suppressor function in BCR-ABL1+ pre-B ALL reveals conserved target genes and biological pathways. The Journal Of Immunology 2016, 196: 122.6-122.6. DOI: 10.4049/jimmunol.196.supp.122.6.Peer-Reviewed Original ResearchTumor suppressor functionTarget genesDevelopmental stage-specific expressionSuppressor functionB cell developmentStem cell signatureZinc fingerHematopoietic developmentIkaros DNAIkaros functionEarly hematopoietic progenitor cellsHematopoietic progenitor cellsRNA sequencingReceptor c-kitMultiple genesBiological functionsInducible expressionTumor suppressionTumor suppressorBiological pathwaysSpecific expressionAdhesion pathwayCritical regulatorIkarosGenes
2015
Ikaros tumor suppressor function in pre-B ALL: potential role of Ikaros target gene Ctnnd1 (IRM10P.621)
Schjerven H, Eggesbo L, Lindeman I, Muschen M. Ikaros tumor suppressor function in pre-B ALL: potential role of Ikaros target gene Ctnnd1 (IRM10P.621). The Journal Of Immunology 2015, 194: 131.19-131.19. DOI: 10.4049/jimmunol.194.supp.131.19.Peer-Reviewed Original ResearchTumor suppressor functionTarget genesSuppressor functionDNA-binding zinc fingersTumor suppressorGenome-wide expression analysisHuman preZinc finger transcription factorFinger transcription factorIndirect target genesDownstream target genesB cell developmentImportant tumor suppressorRole of IkarosProper hematopoiesisZinc fingerChIP-seqRNA-seqTranscription factorsPatient-derived preExpression analysisPotential roleIkarosGenesIkaros expression
2014
Enhanced suppressor function of TIM‐3+FoxP3+ regulatory T cells
Gautron A, Dominguez-Villar M, de Marcken M, Hafler DA. Enhanced suppressor function of TIM‐3+FoxP3+ regulatory T cells. European Journal Of Immunology 2014, 44: 2703-2711. PMID: 24838857, PMCID: PMC4165702, DOI: 10.1002/eji.201344392.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCell DifferentiationCTLA-4 AntigenFemaleForkhead Transcription FactorsGene Expression RegulationGranzymesHepatitis A Virus Cellular Receptor 2HumansInterleukin 1 Receptor Antagonist ProteinInterleukin-10InterleukinsLymphocyte Activation Gene 3 ProteinMaleMembrane ProteinsMiceMinor Histocompatibility AntigensReceptors, CCR6STAT3 Transcription FactorT-Lymphocytes, RegulatoryTh17 CellsConceptsTim-3 expressionRegulatory T cellsTreg cellsTim-3T cellsNatural regulatory T cellsMucin domain 3Number of TIMTh17 cell responseEffector T cellsT cell suppressionHuman Treg cellsT-cell immunoglobulinAnti-CD28 stimulationT cell differentiationSTAT-3 expressionPathogenic Th1Th17 cellsTc1 cellsImmune toleranceTh1 cellsLevel of expressionReduced gene expressionGene expressionSuppressor function
2012
PKCε Promotes Oncogenic Functions of ATF2 in the Nucleus while Blocking Its Apoptotic Function at Mitochondria
Lau E, Kluger H, Varsano T, Lee K, Scheffler I, Rimm DL, Ideker T, Ronai ZA. PKCε Promotes Oncogenic Functions of ATF2 in the Nucleus while Blocking Its Apoptotic Function at Mitochondria. Cell 2012, 148: 543-555. PMID: 22304920, PMCID: PMC3615433, DOI: 10.1016/j.cell.2012.01.016.Peer-Reviewed Original ResearchConceptsTumor suppressor functionGenotoxic stressNuclear exportSuppressor functionTranscription factor ATF2Tumor suppressor activityApoptotic functionSubcellular localizationMelanoma tumor samplesNuclear localizationMitochondrial permeabilityOncogenic functionOncogenic activityATF2MitochondriaPKCε levelsSuppressor activityMembrane permeabilityMelanoma cellsPKCεApoptosisTumor samplesLocalization
2010
HER2 Silences Tumor Suppression in Breast Cancer Cells by Switching Expression of C/EBPβ Isoforms
Arnal-Estapé A, Tarragona M, Morales M, Guiu M, Nadal C, Massagué J, Gomis R. HER2 Silences Tumor Suppression in Breast Cancer Cells by Switching Expression of C/EBPβ Isoforms. Cancer Research 2010, 70: 9927-9936. PMID: 21098707, DOI: 10.1158/0008-5472.can-10-0869.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBlotting, WesternBreast NeoplasmsCCAAT-Enhancer-Binding Protein-betaCell LineCell Line, TumorCellular SenescenceGene Expression Regulation, NeoplasticHumansIn Situ Hybridization, FluorescenceMiceMice, NudePhosphorylationPromoter Regions, GeneticProtein BindingProtein BiosynthesisProtein IsoformsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mycReceptor, ErbB-2Reverse Transcriptase Polymerase Chain ReactionRNA InterferenceTransforming Growth Factor betaTrastuzumabConceptsBreast cancer cellsTumor suppressionBreast cancerOncogene-induced senescenceCancer cellsHER2-overexpressing breast cancer cellsSubtypes of breast cancerHER2 antibody trastuzumabTransforming growth factor-bBreast cancer developmentGrowth factor BTranscriptional repressor complexHER2 signalingSuppressor responseTumor progressionMammary epithelial cellsAntibody trastuzumabHER2Cancer developmentEpithelial cellsSuppressor functionSwitching expressionInterfere with activitiesMYC promoterBreast
2009
Inactivation of Pre-B Cell Receptor-Mediated Tumor Suppression by Aberrant Splicing in Ph+ Acute Lymphoblastic Leukemia.
Duy C, Sprangers M, Klemm L, Nahar R, Nowak D, Martinelli G, Hofmann W, Koeffler P, Jumaa H, Müschen M. Inactivation of Pre-B Cell Receptor-Mediated Tumor Suppression by Aberrant Splicing in Ph+ Acute Lymphoblastic Leukemia. Blood 2009, 114: 579. DOI: 10.1182/blood.v114.22.579.579.Peer-Reviewed Original ResearchPre-B cell receptorSH2 domainSplice factorsTumor suppressor functionAberrant splicingSplice variantsPre-B cell receptor signalingSequence analysisSplice siteSplice site mutationExon 16Suppressor functionCell receptorImportant protein domainsFunctional SH2 domainSite mutationSplice site selectionDetailed sequence analysisCell receptor signalingDominant negative effectDownstream effector moleculesCell linesMultiple splice variantsSplicing factorsProtein domainsSrc phosphorylation of RhoGDI2 regulates its metastasis suppressor function
Wu Y, Moissoglu K, Wang H, Wang X, Frierson HF, Schwartz MA, Theodorescu D. Src phosphorylation of RhoGDI2 regulates its metastasis suppressor function. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 5807-5812. PMID: 19321744, PMCID: PMC2667073, DOI: 10.1073/pnas.0810094106.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorDisease ProgressionGene Expression ProfilingGuanine Nucleotide Dissociation InhibitorsHumansImmunohistochemistryNeoplasm MetastasisPhosphorylationProtein Bindingrho Guanine Nucleotide Dissociation Inhibitor betarho-Specific Guanine Nucleotide Dissociation Inhibitorssrc-Family KinasesTumor Suppressor ProteinsUrinary Bladder NeoplasmsConceptsMetastasis suppressionSrc levelsSrc phosphorylation siteProtein interaction analysisMetastasis suppressor functionRhoGDI2 expressionSuppressor of metastasisGene expression profilingRhoGDI2 functionTyr-153Kinase bindsPhosphorylation sitesAmount of Rac1Expression profilingInteraction partnersSrc phosphorylationSrc inhibitorStable expressionBladder cancerSuppressor functionRhoGDI2Cancer cell linesCell membraneSrcPhosphorylation
2006
Suppression of Insulin Receptor Substrate 1 (IRS-1) Promotes Mammary Tumor Metastasis
Ma Z, Gibson S, Byrne M, Zhang J, White M, Shaw L. Suppression of Insulin Receptor Substrate 1 (IRS-1) Promotes Mammary Tumor Metastasis. Molecular And Cellular Biology 2006, 26: 9338-9351. PMID: 17030605, PMCID: PMC1698550, DOI: 10.1128/mcb.01032-06.Peer-Reviewed Original ResearchConceptsIRS-1Insulin receptor substrate (IRS) proteinsInsulin receptor substrate-1Wild-type levelsMetastasis suppressor functionReceptor substrate-1Cell surface receptorsBreast cancerSubstrate proteinsCytoplasmic adaptorAkt/mTOR activityMammary tumor metastasisSignificant homologySerine phosphorylationDistinct functionsSubstrate-1Mammary tumorsIRS-2MTOR activitySuppressor functionMetastatic mammary tumorsTumor cellsIR-1Surface receptorsBreast cancer metastasis
2005
HIN-1, an Inhibitor of Cell Growth, Invasion, and AKT Activation
Krop I, Parker MT, Bloushtain-Qimron N, Porter D, Gelman R, Sasaki H, Maurer M, Terry MB, Parsons R, Polyak K. HIN-1, an Inhibitor of Cell Growth, Invasion, and AKT Activation. Cancer Research 2005, 65: 9659-9669. PMID: 16266985, DOI: 10.1158/0008-5472.can-05-1663.Peer-Reviewed Original ResearchConceptsTumor suppressor functionHIN-1Suppressor functionMitogen-induced phosphorylationCell growthPotential tumor suppressor functionAnchorage-independent cell growthCell cycle reentryActivation of AktCell cycle arrestActivates AktRetinoblastoma proteinHIN-1 geneGrowth arrestAkt activationRb phosphorylationApparent cell cycle arrestLigand-binding studiesCell migrationCycle arrestPhosphorylationAktEpithelial cellsProteinPotent inhibitor
1990
Yeast suppressor mutations and transfer RNA processing
Nichols M, Willis I, Söll D. Yeast suppressor mutations and transfer RNA processing. Methods In Enzymology 1990, 181: 377-394. PMID: 2199758, DOI: 10.1016/0076-6879(90)81137-j.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBlotting, NorthernChromosomes, FungalGenes, FungalIndicators and ReagentsMolecular Sequence DataMutationNucleic Acid ConformationNucleic Acid HybridizationRNA Polymerase IIIRNA Processing, Post-TranscriptionalRNA, TransferRNA, Transfer, SerSaccharomyces cerevisiaeSuppression, GeneticTranscription FactorsTranscription, GeneticConceptsTRNA genesMature-sized tRNAsRNA processing reactionsPrimer-directed mutagenesisAminoacyl-tRNA synthetaseTransfer RNA moleculesCognate aminoacyl-tRNA synthetaseRNA processingSuppressor mutationsTRNA locusElongation factorProtein biosynthesisRibosomal interactionsRNA moleculesMutant strainStructural proteinsPink coloniesTranscription efficiencyProcessing reactionsProtein synthesisSuppressor functionTRNALow template concentrationsGenesLoci
1988
Loss of functional suppression is linked to decreases in circulating suppressor inducer (CD4 + 2H4 +) T Cells in multiple sclerosis
Chofflon M, Weiner H, Morimoto C, Hafler D. Loss of functional suppression is linked to decreases in circulating suppressor inducer (CD4 + 2H4 +) T Cells in multiple sclerosis. Annals Of Neurology 1988, 24: 185-191. PMID: 2972249, DOI: 10.1002/ana.410240203.Peer-Reviewed Original ResearchConceptsSuppressor-inducer T cellsProgressive multiple sclerosisInducer T cellsSuppressor T cellsMultiple sclerosisT cellsFunctional suppressionTwo-color immunofluorescenceImmunoregulatory abnormalitiesImmunological findingsIgG synthesisMononuclear cellsPokeweed mitogenImmunoglobulin synthesisNormal subjectsSclerosisCD4Neurological diseasesAMLRPatientsTwo-stage assaySuppressor functionSignificant correlationPresent studyCells
1986
Functional complementation between mutations in a yeast suppressor tRNA gene reveals potential for evolution of tRNA sequences.
Willis I, Nichols M, Chisholm V, Söll D, Heyer W, Szankasi P, Amstutz H, Munz P, Kohli J. Functional complementation between mutations in a yeast suppressor tRNA gene reveals potential for evolution of tRNA sequences. Proceedings Of The National Academy Of Sciences Of The United States Of America 1986, 83: 7860-7864. PMID: 3532123, PMCID: PMC386822, DOI: 10.1073/pnas.83.20.7860.Peer-Reviewed Original ResearchConceptsMutant tRNA precursorS. pombe genesSuppressor tRNA geneNucleotide sequence evolutionRNA processing levelRNase P cleavagePombe geneTRNA genesFunctional complementationComplementation eventsS. pombeCycle of inactivationTRNA sequencesTRNA precursorsSequence evolutionSaccharomyces cerevisiaeS. cerevisiaePombe strainSchizosaccharomyces pombe strainStructural domainsDifferential expressionSuppressor functionP cleavageGenesSuppressor
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