2017
ASK1-dependent endothelial cell activation is critical in ovarian cancer growth and metastasis
Yin M, Zhou HJ, Zhang J, Lin C, Li H, Li X, Li Y, Zhang H, Breckenridge DG, Ji W, Min W. ASK1-dependent endothelial cell activation is critical in ovarian cancer growth and metastasis. JCI Insight 2017, 2: e91828. PMID: 28931753, PMCID: PMC5621912, DOI: 10.1172/jci.insight.91828.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationFemaleMAP Kinase Kinase Kinase 5MiceMice, Inbred C57BLMice, KnockoutMice, NudeNeoplasm MetastasisOvarian NeoplasmsPeritoneal NeoplasmsConceptsTumor-associated macrophagesOvarian cancer growthOvarian cancerTranscoelomic metastasisCancer growthTumor growthOrthotopic ovarian cancer modelPeritoneal tumor growthInflammation-mediated tumorigenesisOvarian cancer modelEndothelial cell activationJunction protein VE-cadherinOvarian cancer progressionTAM infiltrationMacrophage infiltrationVascular leakageMacrophage transmigrationVascular permeabilityMouse modelVascular endotheliumMetastasis cancerTherapeutic targetMacrophage activationColon cancerCancer model
2015
Thioredoxin-2 Inhibits Mitochondrial Reactive Oxygen Species Generation and Apoptosis Stress Kinase-1 Activity to Maintain Cardiac Function
Huang Q, Zhou HJ, Zhang H, Huang Y, Hinojosa-Kirschenbaum F, Fan P, Yao L, Belardinelli L, Tellides G, Giordano FJ, Budas GR, Min W. Thioredoxin-2 Inhibits Mitochondrial Reactive Oxygen Species Generation and Apoptosis Stress Kinase-1 Activity to Maintain Cardiac Function. Circulation 2015, 131: 1082-1097. PMID: 25628390, PMCID: PMC4374031, DOI: 10.1161/circulationaha.114.012725.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardiomegalyCells, CulturedHumansMAP Kinase Kinase Kinase 5MiceMice, KnockoutMitochondria, HeartReactive Oxygen SpeciesThioredoxinsConceptsMitochondrial reactive oxygen species generationReactive oxygen species generationOxygen species generationASK1-dependent apoptosisMitochondrial reactive oxygen species productionPhosphorylation/activityKey mitochondrial proteinsSpecies generationMitochondrial membrane depolarizationKinase 1 activityMitochondrial proteinsReactive oxygen species productionCellular redoxMitochondrial Trx2Inhibition of ASK1Apoptotic signalingOxygen species productionThioredoxin 2Protein expression levelsKinase 1ATP productionASK1 inhibitionKnockout miceMitochondrial ultrastructureASK1 inhibitors
2009
DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell survival and apoptosis
Xie D, Gore C, Zhou J, Pong RC, Zhang H, Yu L, Vessella RL, Min W, Hsieh JT. DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell survival and apoptosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 19878-19883. PMID: 19903888, PMCID: PMC2785260, DOI: 10.1073/pnas.0908458106.Peer-Reviewed Original ResearchConceptsDAB2IP proteinCell survivalDeath-signaling moleculePI3K-Akt activityPI3K-Akt activationMetastatic prostate cancer cellsPI3K-Akt pathwayCell cycle arrestASK1 activityScaffold proteinPotent growth inhibitorDeath signalsC2 domainSignal moleculesASK1 activationFunctional analysisCell homeostasisApoptotic defectsConstitutive activationJNK pathwayProstate cancer cellsASK1 pathwayPI3K-AktDAB2IP expressionCycle arrestJAK2 and SHP2 Reciprocally Regulate Tyrosine Phosphorylation and Stability of Proapoptotic Protein ASK1*
Yu L, Min W, He Y, Qin L, Zhang H, Bennett AM, Chen H. JAK2 and SHP2 Reciprocally Regulate Tyrosine Phosphorylation and Stability of Proapoptotic Protein ASK1*. Journal Of Biological Chemistry 2009, 284: 13481-13488. PMID: 19287004, PMCID: PMC2679448, DOI: 10.1074/jbc.m809740200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell LineEndothelial CellsEnzyme StabilityHumansInterferon-gammaJanus Kinase 2MAP Kinase Kinase Kinase 5MiceMice, KnockoutMultienzyme ComplexesMutationPhosphorylationProtein Tyrosine Phosphatase, Non-Receptor Type 11Signal TransductionSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling ProteinsTumor Necrosis Factor-alphaConceptsTyrosine phosphorylationSubstrate-trapping mutantProtein tyrosine phosphatase 2Phosphatase-inactive mutantProteasomal inhibitor MG132ASK1-JNK signalingEndothelial cellsJAK2-specific inhibitorIFN-gamma-induced tyrosine phosphorylationASK1 degradationASK1 dephosphorylationInactive mutantMouse endothelial cellsASK1 phosphorylationPhosphatase 2Inhibitor MG132SHP2Wild typeASK1DephosphorylationMutantsPhosphorylationEnhanced associationJAK2EC apoptosisEndothelial-Specific Expression of Mitochondrial Thioredoxin Promotes Ischemia-Mediated Arteriogenesis and Angiogenesis
Dai S, He Y, Zhang H, Yu L, Wan T, Xu Z, Jones D, Chen H, Min W. Endothelial-Specific Expression of Mitochondrial Thioredoxin Promotes Ischemia-Mediated Arteriogenesis and Angiogenesis. Arteriosclerosis Thrombosis And Vascular Biology 2009, 29: 495-502. PMID: 19150880, PMCID: PMC2734510, DOI: 10.1161/atvbaha.108.180349.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisArteriesBlood Flow VelocityCell MovementDisease Models, AnimalEndothelial CellsHindlimbIschemiaJNK Mitogen-Activated Protein KinasesMaleMAP Kinase Kinase Kinase 5MiceMice, TransgenicMitochondriaMuscle, SkeletalNeovascularization, PhysiologicNitric OxideOxidative StressReactive Oxygen SpeciesRegional Blood FlowSignal TransductionThioredoxinsTime FactorsConceptsEndothelial cellsFlow recoveryFemoral artery ligation modelIschemia-mediated arteriogenesisIschemic reserve capacityLimb perfusion recoveryENOS-deficient miceENOS-KO miceNitric oxide bioavailabilityIschemia-induced angiogenesisEC apoptosisArtery ligation modelEC survivalENOS deletionNontransgenic littermatesStress-induced activationLigation modelPerfusion recoveryLower limbsUpper limbEndothelial-specific expressionSevere impairmentMajor antioxidant proteinsIschemiaMice
2008
AIP1 Recruits Phosphatase PP2A to ASK1 in Tumor Necrosis Factor–Induced ASK1-JNK Activation
Min W, Lin Y, Tang S, Yu L, Zhang H, Wan T, Luhn T, Fu H, Chen H. AIP1 Recruits Phosphatase PP2A to ASK1 in Tumor Necrosis Factor–Induced ASK1-JNK Activation. Circulation Research 2008, 102: 840-848. PMID: 18292600, DOI: 10.1161/circresaha.107.168153.Peer-Reviewed Original ResearchConceptsASK1-JNK signalingASK1 dephosphorylationAssociation of PP2APP2A catalytic subunitCatalytic inactive formPP2A inhibitor okadaicASK1-JNK activationC-Jun N-terminal kinaseActivation of JNKEndothelial cellsN-terminal kinasePhosphatase PP2ACritical rolePotential phosphataseProtein phosphataseGAP domainInhibitor okadaicProtein familyCatalytic subunitC2 domainPP2AAIP1Novel memberApoptotic signalingRNA knockdownAIP1 Is Critical in Transducing IRE1-mediated Endoplasmic Reticulum Stress Response*
Luo D, He Y, Zhang H, Yu L, Chen H, Xu Z, Tang S, Urano F, Min W. AIP1 Is Critical in Transducing IRE1-mediated Endoplasmic Reticulum Stress Response*. Journal Of Biological Chemistry 2008, 283: 11905-11912. PMID: 18281285, PMCID: PMC2335342, DOI: 10.1074/jbc.m710557200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCattleDimerizationDNA-Binding ProteinsEndoplasmic ReticulumEndothelial CellsEnzyme ActivationHumansJNK Mitogen-Activated Protein KinasesMAP Kinase Kinase Kinase 5Membrane ProteinsMiceMice, KnockoutProtein BindingProtein Serine-Threonine KinasesProtein Structure, TertiaryRas GTPase-Activating ProteinsRegulatory Factor X Transcription FactorsSignal TransductionTranscription FactorsX-Box Binding Protein 1ConceptsASK1-interacting protein-1SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis
Li X, Luo Y, Yu L, Lin Y, Luo D, Zhang H, He Y, Kim YO, Kim Y, Tang S, Min W. SENP1 mediates TNF-induced desumoylation and cytoplasmic translocation of HIPK1 to enhance ASK1-dependent apoptosis. Cell Death & Differentiation 2008, 15: 739-750. PMID: 18219322, DOI: 10.1038/sj.cdd.4402303.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsAntioxidantsApoptosisCarrier ProteinsCattleCells, CulturedCysteine EndopeptidasesCytoplasmEndopeptidasesEndothelial CellsFibroblastsHumansMAP Kinase Kinase Kinase 5MiceMice, KnockoutMutationProtein KinasesProtein Processing, Post-TranslationalProtein Serine-Threonine KinasesProtein TransportReactive Oxygen SpeciesRecombinant ProteinsRNA InterferenceRNA, Small InterferingSignal TransductionSmall Ubiquitin-Related Modifier ProteinsThioredoxinsTime FactorsTransfectionTumor Necrosis Factor-alphaConceptsASK1-dependent apoptosisASK1-JNK activationCytoplasmic translocationMouse embryonic fibroblast cellsNuclear translocationSUMO-specific proteasesWild-type formEmbryonic fibroblast cellsNuclear importAntioxidant protein thioredoxinHIPK1Mutant formsEndothelial cellsDeSUMOylationProtein thioredoxinSubsequent cytoplasmic translocationSENP1TranslocationCritical functionsThioredoxinFibroblast cellsApoptosisCellsActivationSUMO
2007
Structural and Functional Characterization of the Human Protein Kinase ASK1
Bunkoczi G, Salah E, Filippakopoulos P, Fedorov O, Müller S, Sobott F, Parker SA, Zhang H, Min W, Turk BE, Knapp S. Structural and Functional Characterization of the Human Protein Kinase ASK1. Structure 2007, 15: 1215-1226. PMID: 17937911, PMCID: PMC2100151, DOI: 10.1016/j.str.2007.08.011.Peer-Reviewed Original ResearchConceptsApoptosis signal-regulating kinase 1Autophosphorylation sitesSignal-regulated kinases 1ASK1 kinase activityVitro autophosphorylation sitesAnalytical ultracentrifugationHigh-resolution structuresATP-mimetic inhibitorSite-directed mutantsReporter gene assayPhosphorylation motifsPhosphorylation sitesCatalytic domainFunctional characterizationKinase activityRegulatory mechanismsKinase 1Tight dimerMimetic inhibitorsGene assayEssential roleSelective inhibitorTail fashionCrystallographic analysisMass spectrometryRIP1-mediated AIP1 Phosphorylation at a 14-3-3-binding Site Is Critical for Tumor Necrosis Factor-induced ASK1-JNK/p38 Activation*
Zhang R, Zhang H, Lin Y, Li J, Pober JS, Min W. RIP1-mediated AIP1 Phosphorylation at a 14-3-3-binding Site Is Critical for Tumor Necrosis Factor-induced ASK1-JNK/p38 Activation*. Journal Of Biological Chemistry 2007, 282: 14788-14796. PMID: 17389591, DOI: 10.1074/jbc.m701148200.Peer-Reviewed Original ResearchMeSH Keywords14-3-3 ProteinsAdaptor Proteins, Signal TransducingAmino Acid SubstitutionAnimalsApoptosisCarrier ProteinsCattleCells, CulturedEndothelial CellsEnzyme ActivationGuanylate KinasesHumansMAP Kinase Kinase 4MAP Kinase Kinase Kinase 5MAP Kinase Signaling SystemMultiprotein ComplexesMutation, MissenseP38 Mitogen-Activated Protein KinasesPhosphorylationProtein BindingProtein Processing, Post-TranslationalProteinsReceptor-Interacting Protein Serine-Threonine KinasesTNF Receptor-Associated Factor 2Tumor Necrosis Factor-alphaConceptsJNK/p38 activationP38 activationTRAF2-ASK1ASK1-JNK activationPhospho-specific antibodiesTNF treatmentEndothelial cellsComplex formationGAP domainProtein familyTerminal domainAIP1Novel memberApoptotic signalingTNF signalingRNA knockdownRIP1PhosphorylationProtein 1ASK1-interacting protein-1EC apoptosisTRAF2ASK1Similar kineticsTumor necrosis factor
2006
SOCS1 Inhibits Tumor Necrosis Factor-induced Activation of ASK1-JNK Inflammatory Signaling by Mediating ASK1 Degradation*
He Y, Zhang W, Zhang R, Zhang H, Min W. SOCS1 Inhibits Tumor Necrosis Factor-induced Activation of ASK1-JNK Inflammatory Signaling by Mediating ASK1 Degradation*. Journal Of Biological Chemistry 2006, 281: 5559-5566. PMID: 16407264, DOI: 10.1074/jbc.m512338200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCattleCells, CulturedEndothelial CellsEnzyme ActivationInflammationIntracellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesMAP Kinase Kinase Kinase 5MiceMice, KnockoutRecombinant Fusion ProteinsRepressor ProteinsSignal TransductionSrc Homology DomainsSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling 3 ProteinSuppressor of Cytokine Signaling ProteinsTumor Necrosis Factor-alphaConceptsASK1 degradationDissociation of ASK1Member of suppressorTumor necrosis factor-induced activationEndothelial cellsActivation of JNKPhosphotyrosine bindingUndergoes ubiquitinationSH2 domainProteasomal inhibitorsASK1 activationNegative regulatorApoptotic responseASK1Cytokine signalingSOCS1 functionsASK1 expressionSOCS1Tumor necrosis factorSignalingSOCS1-deficient mice
2004
AIP1/DAB2IP, a Novel Member of the Ras-GAP Family, Transduces TRAF2-induced ASK1-JNK Activation*
Zhang H, Zhang R, Luo Y, D'Alessio A, Pober JS, Min W. AIP1/DAB2IP, a Novel Member of the Ras-GAP Family, Transduces TRAF2-induced ASK1-JNK Activation*. Journal Of Biological Chemistry 2004, 279: 44955-44965. PMID: 15310755, DOI: 10.1074/jbc.m407617200.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCarrier ProteinsCattleCell LineCell MembraneCytoplasmGene DeletionGenes, ReporterGuanylate KinasesHumansImmunoblottingImmunoprecipitationJNK Mitogen-Activated Protein KinasesMAP Kinase Kinase 4MAP Kinase Kinase Kinase 5Microscopy, ConfocalMicroscopy, FluorescenceMitogen-Activated Protein Kinase KinasesModels, BiologicalMutationNF-kappa BProlineProtein Structure, TertiaryProtein TransportProteinsRas GTPase-Activating ProteinsSignal TransductionTNF Receptor-Associated Factor 2Transfection