2023
Ectopic RING activity at the ER membrane differentially impacts ERAD protein quality control pathways
Mehrtash A, Hochstrasser M. Ectopic RING activity at the ER membrane differentially impacts ERAD protein quality control pathways. Journal Of Biological Chemistry 2023, 299: 102927. PMID: 36682496, PMCID: PMC9950527, DOI: 10.1016/j.jbc.2023.102927.Peer-Reviewed Original ResearchConceptsEndoplasmic reticulum-associated degradationProtein quality control pathwaysQuality control pathwaysER membraneE3 complexControl pathwaysRING-type E3 ubiquitin ligasesE3 ubiquitin ligasesDominant negative mutantDoa10 substratesMisfolded proteinsUbiquitin ligasesERAD factorsMammalian cellsRING domainUBC6Substrate turnoverLuminal substratesDoa10OverexpressionPathway defectsYeastPathwayRing activityMembrane
2018
Simultaneous Targeting of PARP1 and RAD52 Triggers Dual Synthetic Lethality in BRCA-Deficient Tumor Cells
Sullivan-Reed K, Bolton-Gillespie E, Dasgupta Y, Langer S, Siciliano M, Nieborowska-Skorska M, Hanamshet K, Belyaeva EA, Bernhardy AJ, Lee J, Moore M, Zhao H, Valent P, Matlawska-Wasowska K, Müschen M, Bhatia S, Bhatia R, Johnson N, Wasik MA, Mazin AV, Skorski T. Simultaneous Targeting of PARP1 and RAD52 Triggers Dual Synthetic Lethality in BRCA-Deficient Tumor Cells. Cell Reports 2018, 23: 3127-3136. PMID: 29898385, PMCID: PMC6082171, DOI: 10.1016/j.celrep.2018.05.034.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBRCA1 ProteinBRCA2 ProteinDNA RepairFemaleFusion Proteins, bcr-ablHomologous RecombinationHumansImatinib MesylateKaplan-Meier EstimateLeukemia, Myeloid, AcuteMaleMiceMice, Inbred NODMice, KnockoutPhthalazinesPiperazinesPoly (ADP-Ribose) Polymerase-1Rad52 DNA Repair and Recombination ProteinSynthetic Lethal MutationsTumor Suppressor p53-Binding Protein 1ConceptsTumor cellsBRCA-deficient tumor cellsSimultaneous targetingBRCA-deficient tumorsClinical trialsProlonged latencyImmunodeficient miceTherapeutic outcomesBRCA1-deficient tumorsPARP inhibitorsBRCA-deficient cellsMinimal toxicitySynergistic activitySynthetic lethal effectTumorsNormal cellsPARPiSynthetic lethalityInhibitorsLethal effectsCellsDominant negative mutantSynergistic accumulationMalignancyTargeting
2016
Enhancement of DEN-induced liver tumorigenesis in heme oxygenase-1 G143H mutant transgenic mice
Jin J, Wang D, Xiao H, Wei H, Matunda C, Zhang H, Li X, Wang C, Zou C, Gao X, Zhao W, Li Q. Enhancement of DEN-induced liver tumorigenesis in heme oxygenase-1 G143H mutant transgenic mice. Biochemical And Biophysical Research Communications 2016, 481: 169-175. PMID: 27810363, DOI: 10.1016/j.bbrc.2016.10.148.Peer-Reviewed Original ResearchConceptsHO-1Susceptibility to DEN-induced hepatocarcinogenesisTransgenic miceHO-1 promoter polymorphismSecretion of inflammatory cytokinesDEN-induced hepatocarcinogenesisMutant transgenic miceHeme oxygenaseProgression of tumorigenesisAnti-inflammatory functionsPromoter polymorphismTumor growthInflammatory cytokinesDominant negative mutantEnhancement of ROS productionLiver carcinogenesisLiver tumorigenesisHepatocyte deathGrowing body of evidenceBody of evidenceTumorigenesisProtective roleROS productionNegative mutantMice
2015
Activating the translational repressor 4E-BP or reducing S6K-GSK3β activity prevents accelerated axon growth induced by hyperactive mTOR in vivo
Gong X, Zhang L, Huang T, Lin TV, Miyares L, Wen J, Hsieh L, Bordey A. Activating the translational repressor 4E-BP or reducing S6K-GSK3β activity prevents accelerated axon growth induced by hyperactive mTOR in vivo. Human Molecular Genetics 2015, 24: 5746-5758. PMID: 26220974, PMCID: PMC4581604, DOI: 10.1093/hmg/ddv295.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAxonsCarrier ProteinsCell Cycle ProteinsCell Growth ProcessesEukaryotic Initiation FactorsFemaleGene Expression RegulationGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaMaleMechanistic Target of Rapamycin Complex 1MiceMultiprotein ComplexesPhosphoproteinsRibosomal Protein S6 Kinases, 90-kDaSignal TransductionTOR Serine-Threonine KinasesConceptsAxon growthNew therapeutic optionsMultiple axon formationTherapeutic optionsHippocampal neuronsHyperactive mTORNeurological disordersUtero electroporationAxonal connectivityGSK3β activityTranslational repressor 4E-BPEukaryotic initiation factor 4EMTOR complex 1Translational targetsInitiation factor 4EHyperactive mTORC1VivoDownstream effectorsGSK3βAxon formationLong-range connectivityDominant negative mutantLithium chlorideMTORopathiesMTORC1
2009
Klf4 Interacts Directly with Oct4 and Sox2 to Promote Reprogramming
Wei Z, Yang Y, Zhang P, Andrianakos R, Hasegawa K, Lyu J, Chen X, Bai G, Liu C, Pera M, Lu W. Klf4 Interacts Directly with Oct4 and Sox2 to Promote Reprogramming. Stem Cells 2009, 27: 2969-2978. PMID: 19816951, DOI: 10.1002/stem.231.Peer-Reviewed Original ResearchConceptsInduced pluripotent stemEndogenous KLF4Sets of transcription factorsInduced pluripotent stem cellsTandem zinc fingerEmbryonic stemDominant negative mutantInduced iPS cellsMouse ES cellsSomatic cell reprogrammingWild-type Klf4Zinc fingerPluripotent stemTranscription factorsC-terminusIPS cellsInhibit reprogrammingEctopic expressionTarget genesNanog promoterSomatic cellsSOX2Cell reprogrammingES cellsKLF4Molecular basis of CD4 repression by the Swi/Snf‐like BAF chromatin remodeling complex
Wan M, Zhang J, Lai D, Jani A, Prestone‐Hurlburt P, Zhao L, Ramachandran A, Schnitzler GR, Chi T. Molecular basis of CD4 repression by the Swi/Snf‐like BAF chromatin remodeling complex. European Journal Of Immunology 2009, 39: 580-588. PMID: 19180471, PMCID: PMC2774848, DOI: 10.1002/eji.200838909.Peer-Reviewed Original ResearchConceptsCD4 repressionCD4 silencerDominant negative mutantBAF complexNegative mutantSWI/SNF-like BAF chromatinBRG1/BRM-associated factor (BAF) chromatinCD4 silencer functionLinker histone H1Factor (BAF) chromatinT cell developmentKey repressorBAF chromatinSilencer functionBAF57Histone H1ChromatinMolecular basisFlanking regionsRepressionTranslational frameCD4 transcriptionSilencerEarly thymocytesMutantsInduction of TLR4-target genes entails calcium/calmodulin-dependent regulation of chromatin remodeling
Lai D, Wan M, Wu J, Preston-Hurlburt P, Kushwaha R, Grundström T, Imbalzano AN, Chi T. Induction of TLR4-target genes entails calcium/calmodulin-dependent regulation of chromatin remodeling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 1169-1174. PMID: 19164553, PMCID: PMC2633529, DOI: 10.1073/pnas.0811274106.Peer-Reviewed Original ResearchConceptsCalcium/CaMChromatin remodelingBAF complexSWI/SNF-like BAF chromatinTarget genesDominant negative mutantCalcium/calmodulinCalmodulin-dependent regulationHMG domainBAF chromatinCaM-binding peptideNegative mutantGene expressionCaM antagonistsGenesToll-like receptor 4ChromatinRegulationRemodelingRecruitmentComplexesBAF57RNAiMutantsInduction
2008
Endogenous RhoG is dispensable for integrin-mediated cell spreading but contributes to Rac-independent migration
Meller J, Vidali L, Schwartz MA. Endogenous RhoG is dispensable for integrin-mediated cell spreading but contributes to Rac-independent migration. Journal Of Cell Science 2008, 121: 1981-1989. PMID: 18505794, PMCID: PMC2759683, DOI: 10.1242/jcs.025130.Peer-Reviewed Original Research
2007
A Specific Subset of Transient Receptor Potential Vanilloid-Type Channel Subunits in Caenorhabditis elegans Endocrine Cells Function as Mixed Heteromers to Promote Neurotransmitter Release
Jose AM, Bany IA, Chase DL, Koelle MR. A Specific Subset of Transient Receptor Potential Vanilloid-Type Channel Subunits in Caenorhabditis elegans Endocrine Cells Function as Mixed Heteromers to Promote Neurotransmitter Release. Genetics 2007, 175: 93-105. PMID: 17057248, PMCID: PMC1774992, DOI: 10.1534/genetics.106.065516.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnimals, Genetically ModifiedBiological TransportCaenorhabditis elegansCaenorhabditis elegans ProteinsEndocrine GlandsFemaleIon ChannelsMolecular Sequence DataNerve Tissue ProteinsNeurosecretory SystemsOvipositionSequence Homology, Amino AcidTRPV Cation ChannelsConceptsOCR-2Neuroendocrine cellsEgg-laying defectsTRPV channel OSM-9Heteromeric channelsG protein GDominant negative mutantTransient receptor potential channelsEndocrine cell functionOSM-9Heteromeric partnerTRPV channelsSensory neuronsSingle knockoutDetectable functionOCR-1Premature eggsSensory transductionChannel subunitsDetectable roleSubunit compositionCell functionRelease of neurotransmittersNeurotransmitter releaseSubunit combinations
2005
A Survivin Gene Signature Predicts Aggressive Tumor Behavior
Salz W, Eisenberg D, Plescia J, Garlick DS, Weiss RM, Wu XR, Sun TT, Altieri DC. A Survivin Gene Signature Predicts Aggressive Tumor Behavior. Cancer Research 2005, 65: 3531-3534. PMID: 15867343, DOI: 10.1158/0008-5472.can-04-4284.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsButylhydroxybutylnitrosamineCarcinogensDisease ProgressionFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansInhibitor of Apoptosis ProteinsMembrane ProteinsMiceMice, TransgenicMicrotubule-Associated ProteinsNeoplasm ProteinsPolymerase Chain ReactionSurvivinTransgenesTumor Suppressor Protein p53Urinary BladderUrinary Bladder NeoplasmsUroplakin IIConceptsTransgenic expressionGene signatureGlobal transcriptional changesDominant negative mutantGene expression profilesSuch genesTumor progressionTranscriptional changesCell divisionEssential regulatorGene expressionExpression profilesTransgenic animalsExtracellular matrixTissue microenvironmentAggressive tumor behaviorPreferential incidenceGenesInflammatory genesSurvivinExpressionTumor behaviorSurvivin expressionAssociated gene signaturesTransgenic model
2003
The Salmonella SpiC protein targets the mammalian Hook3 protein function to alter cellular trafficking
Shotland Y, Krämer H, Groisman EA. The Salmonella SpiC protein targets the mammalian Hook3 protein function to alter cellular trafficking. Molecular Microbiology 2003, 49: 1565-1576. PMID: 12950921, DOI: 10.1046/j.1365-2958.2003.03668.x.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBacterial ProteinsCell LineCyclic AMPGenes, ReporterLysosomesMacrophagesMiceMicroscopy, FluorescenceMicrotubule-Associated ProteinsMolecular Sequence DataPhagosomesProtein BindingProtein TransportRecombinant Fusion ProteinsSalmonella typhimuriumSequence Homology, Amino AcidConceptsPhagosome-lysosome fusionCellular traffickingType III secretion systemEndosome-endosome fusionDominant negative mutantCytosol of macrophagesMammalian proteinsPhenotype of cellsProtein functionGolgi morphologySecretion systemDistribution of lysosomesSpiC genePhagosomal membraneProteinMurine macrophagesTraffickingCytosolVero cellsMacrophagesCellsMutantsHook3FusionGenes
2002
AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation
Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 15983-15987. PMID: 12444247, PMCID: PMC138551, DOI: 10.1073/pnas.252625599.Peer-Reviewed Original ResearchMeSH KeywordsAdenine NucleotidesAdenylate KinaseAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein Kinase Type 4Calcium-Calmodulin-Dependent Protein KinasesEnergy MetabolismEnzyme InductionGene Expression RegulationGenes, DominantGuanidinesMiceMice, TransgenicMitochondria, MuscleMuscle ProteinsMuscle, SkeletalPhosphocreatinePropionatesTranscription FactorsConceptsMitochondrial biogenesisPeroxisome proliferator-activated receptor-gamma coactivator-1alphaDominant negative mutantProliferator-activated receptor-gamma coactivator-1alphaRole of AMPReceptor-gamma coactivator-1alphaGamma coactivator-1alphaProtein kinaseAMPK inactivationEnergy deprivationBiogenesisAMPK activityDN-AMPKMuscle AMPKCritical adaptationKinase IVCritical regulatorAMP kinaseCoactivator-1alphaMitochondrial contentAMPKFuel sensorEnergy statusKinase
2000
Protein folding and deficiencies caused by dominant-negative mutants of hormones
Dannies P. Protein folding and deficiencies caused by dominant-negative mutants of hormones. Vitamins & Hormones 2000, 58: 1-26. PMID: 10668393, DOI: 10.1016/s0083-6729(00)58019-4.Peer-Reviewed Original Research
1999
Expression and Targeting of the Apoptosis Inhibitor, Survivin, in Human Melanoma
Grossman D, McNiff J, Li F, Altieri D. Expression and Targeting of the Apoptosis Inhibitor, Survivin, in Human Melanoma. Journal Of Investigative Dermatology 1999, 113: 1076-1081. PMID: 10594755, DOI: 10.1046/j.1523-1747.1999.00776.x.Peer-Reviewed Original ResearchConceptsInvasive malignant melanomaMalignant melanomaDominant negative mutantCultured normal human melanocytesCell cycle progressionApoptosis inhibitor Bcl-2G1 DNA contentNormal human melanocytesSurvivin expressionApoptosis inhibitor survivinApoptosis regulationEndogenous survivinNegative mutantTwo-color flow cytometryGenotoxic stimuliMalignant melanoma cell linesSurvivin dominant-negative mutantCycle progressionMetastatic malignant melanomaApoptosis inhibitorMelanoma cell linesHuman melanocytesMIB-1 stainingApoptosis inhibitionCases of nevusInhibition of Allergic Inflammation in a Murine Model of Asthma by Expression of a Dominant-Negative Mutant of GATA-3
Zhang D, Yang L, Cohn L, Parkyn L, Homer R, Ray P, Ray A. Inhibition of Allergic Inflammation in a Murine Model of Asthma by Expression of a Dominant-Negative Mutant of GATA-3. Immunity 1999, 11: 473-482. PMID: 10549629, DOI: 10.1016/s1074-7613(00)80122-3.Peer-Reviewed Original ResearchMeSH KeywordsAerosolsAmino Acid SubstitutionAnimalsAsthmaBronchoalveolar Lavage FluidDNA-Binding ProteinsDrug HypersensitivityEosinophiliaGATA3 Transcription FactorGene Expression RegulationGenes, DominantImmunizationImmunoglobulin EInflammationInterleukin-13Interleukin-4Interleukin-5LungMiceMice, Inbred C57BLMice, TransgenicMucusMutagenesis, Site-DirectedOvalbuminTh2 CellsTrans-ActivatorsConceptsCytokines IL-4GATA-3IL-13IL-4IL-5Th2 cytokines IL-4Pathogenesis of asthmaTreatment of asthmaTranscription factor GATA-3Potential therapeutic targetAirway eosinophiliaTh2 responsesAllergic inflammationAllergic diseasesTh2 cytokinesT-cell-specific fashionTh1 cellsIgE synthesisTh2 cellsMucus productionMurine modelTherapeutic targetTransgenic miceAsthmaDominant negative mutantDishevelled Proteins Lead to Two Signaling Pathways REGULATION OF LEF-1 AND c-Jun N-TERMINAL KINASE IN MAMMALIAN CELLS*
Li L, Yuan H, Xie W, Mao J, Caruso A, McMahon A, Sussman D, Wu D. Dishevelled Proteins Lead to Two Signaling Pathways REGULATION OF LEF-1 AND c-Jun N-TERMINAL KINASE IN MAMMALIAN CELLS*. Journal Of Biological Chemistry 1999, 274: 129-134. PMID: 9867820, DOI: 10.1074/jbc.274.1.129.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAdaptor Proteins, Signal TransducingAnimalsbeta CateninCalcium-Calmodulin-Dependent Protein KinasesCell Cycle ProteinsCOS CellsCytoskeletal ProteinsDishevelled ProteinsDNA-Binding ProteinsEnzyme ActivationJNK Mitogen-Activated Protein KinasesLymphoid Enhancer-Binding Factor 1MiceMitogen-Activated Protein KinasesPhosphoproteinsSignal TransductionTrans-ActivatorsTranscription FactorsTranscription, GeneticUp-RegulationConceptsJNK activationMammalian cellsT-cell factorSmall G proteinsC-Jun N-terminal kinaseDominant negative mutantBeta-catenin levelsDifferent signaling pathwaysCOS-7 cellsN-terminal kinaseC-Jun NDishevelled proteinsDvl proteinsDEP domainDependent transcriptionNegative mutantPathway regulationKinase activityLEF-1Transcription activitySignaling pathwaysG proteinsNovel pathwayCell factorProtein
1998
Regulation of Secretion of Alzheimer Amyloid Precursor Protein by the Mitogen‐Activated Protein Kinase Cascade
Desdouits‐Magnen J, Desdouits F, Takeda S, Syu L, Saltiel A, Buxbaum J, Czernik A, Nairn A, Greengard P. Regulation of Secretion of Alzheimer Amyloid Precursor Protein by the Mitogen‐Activated Protein Kinase Cascade. Journal Of Neurochemistry 1998, 70: 524-530. PMID: 9453546, DOI: 10.1046/j.1471-4159.1998.70020524.x.Peer-Reviewed Original ResearchMeSH KeywordsAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsCalcium-Calmodulin-Dependent Protein KinasesCarbacholCHO CellsCOS CellsCricetinaeEnzyme ActivationEnzyme InhibitorsFlavonoidsHumansIndolesMaleimidesMitogen-Activated Protein Kinase KinasesMuscarinic AgonistsNerve Growth FactorsPC12 CellsPhorbol 12,13-DibutyrateProtein Kinase InhibitorsProtein KinasesRatsReceptor, Muscarinic M1Receptors, MuscarinicConceptsProtein kinase CAlzheimer amyloid precursor proteinKinase cascadeM1 muscarinic receptor stimulationMitogen-activated protein kinase cascadeProtein kinase cascadeMAP kinase cascadeMAP kinase kinaseMAP kinase-independent pathwayMitogen-activated protein kinase kinase activationDominant negative mutantPrecursor proteinDistinct secretory pathwaysPKC-independent pathwayStimulation of PKCAmyloid precursor proteinKinase-independent pathwaySAPP secretionKinase kinaseSecretory pathwayNegative mutantMAP kinaseKinase activationRegulation of secretionPD 98059
1997
Interaction of wild type and dominant-negative p55PIK regulatory subunit of phosphatidylinositol 3-kinase with insulin-like growth factor-1 signaling proteins.
Mothe I, Delahaye L, Filloux C, Pons S, White M, Van Obberghen E. Interaction of wild type and dominant-negative p55PIK regulatory subunit of phosphatidylinositol 3-kinase with insulin-like growth factor-1 signaling proteins. Endocrinology 1997, 11: 1911-23. PMID: 9415396, DOI: 10.1210/mend.11.13.0029.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesBiological TransportFungal ProteinsGenes, ReporterGlucoseInsulinInsulin Receptor Substrate ProteinsInsulin-Like Growth Factor IMutagenesis, Site-DirectedPhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationPrecipitin TestsReceptor, IGF Type 1Recombinant Fusion ProteinsSaccharomyces cerevisiaeSignal TransductionConceptsTwo-hybrid systemInsulin receptor substrate-1Receptor substrate-1Regulatory subunitSubstrate-1Src homology 2 domainInter-SH2 domainProtein-protein interactionsInhibitor of PIAmino acids 203Dominant negative mutantInsulin-stimulated glucose transportIGF-IRInsulin-like growth factor 1 receptorNH2 terminus regionDominant negative actionGrowth factor 1 receptorP110alpha catalytic subunitIGF-I stimulationSH2 domainFactor 1 receptorCatalytic subunitTyrosine phosphorylationWild typeP55PIKSuppression of autocrine cell proliferation and tumorigenesis of human melanoma cells and fibroblast growth factor transformed fibroblasts by a kinase-deficient FGF receptor 1: evidence for the involvement of Src-family kinases
Yayon A, Ma Y, Safran M, Klagsbrun M, Halaban R. Suppression of autocrine cell proliferation and tumorigenesis of human melanoma cells and fibroblast growth factor transformed fibroblasts by a kinase-deficient FGF receptor 1: evidence for the involvement of Src-family kinases. Oncogene 1997, 14: 2999-3009. PMID: 9223663, DOI: 10.1038/sj.onc.1201159.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsCell DivisionCell Line, TransformedFibroblast Growth Factor 2FibroblastsFilaggrin ProteinsGenes, DominantHumansMelanomaMicePhenotypeProtein-Tyrosine KinasesReceptor Protein-Tyrosine KinasesReceptor, Fibroblast Growth Factor, Type 1Receptors, Fibroblast Growth FactorRecombinant Proteinssrc Homology DomainsTumor Cells, CulturedConceptsSrc family kinasesFGF receptor 1FGF receptorsTyrosyl-phosphorylated proteinsHuman melanoma cellsMelanoma cellsImmune kinase assayIntracellular kinase domainDominant negative mutantActivated FGF receptorCell proliferationMetastatic melanoma cellsMelanoma tumor progressionGrowth factorTransmembrane domainKinase assaysSrc familyKinase domainDownstream targetsReceptor 1Fibroblast growth factorBasic fibroblast growth factorGrowth advantageNormal melanocytesAutocrine activation
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