Featured Publications
Polo-like Kinase 1 and Chk2 Interact and Co-localize to Centrosomes and the Midbody*
Tsvetkov L, Xu X, Li J, Stern DF. Polo-like Kinase 1 and Chk2 Interact and Co-localize to Centrosomes and the Midbody*. Journal Of Biological Chemistry 2002, 278: 8468-8475. PMID: 12493754, DOI: 10.1074/jbc.m211202200.Peer-Reviewed Original ResearchConceptsPhosphorylation of Chk2Polo-like kinase 1Thr-68DNA damageSimilar subcellular localization patternsDNA damage checkpoint pathwayKinase 1Damage checkpoint pathwaySubcellular localization patternsChromosome segregationMitotic exitLate mitosisNuclear fociMitotic entryIndirect immunofluorescence microscopyMitotic checkpointSer-28Early mitosisCheckpoint pathwayChk2Localization patternsCentrosomesThr-26Immunofluorescence microscopyMidbodyNFBD1/KIAA0170 Is a Chromatin-associated Protein Involved in DNA Damage Signaling Pathways*
Xu X, Stern DF. NFBD1/KIAA0170 Is a Chromatin-associated Protein Involved in DNA Damage Signaling Pathways*. Journal Of Biological Chemistry 2002, 278: 8795-8803. PMID: 12499369, DOI: 10.1074/jbc.m211392200.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceBase SequenceCell Cycle ProteinsChromatinDNA DamageDNA PrimersDNA ReplicationDNA-Binding ProteinsFluorescent Antibody Technique, IndirectG2 PhaseHeLa CellsHumansMitosisMolecular Sequence DataNuclear ProteinsPhosphorylationSequence Homology, Amino AcidSignal TransductionTrans-ActivatorsConceptsN-terminal FHA domainChromatin-associated proteinsDNA damageDNA Damage Signaling PathwayDNA double-strand breaksDiscrete nuclear fociDNA damage responseNumber of proteinsDouble-strand breaksBRCT domainFHA domainGamma-H2AX fociNuclear fociRad50 fociDamage responseDNA repairNFBD1Signaling pathwaysTandem repeatsProteinNuclear factorUntreated cellsHydroxyurea treatmentPathwayDiffuse nuclear staining
2018
Keeping Tumors Out of the MAPK Fitness Zone
Stern DF. Keeping Tumors Out of the MAPK Fitness Zone. Cancer Discovery 2018, 8: 20-23. PMID: 29311225, DOI: 10.1158/2159-8290.cd-17-1243.Peer-Reviewed Original ResearchConceptsMAPK-targeted therapiesGreater fitnessMAPK signalingTumor cell subclonesMAPK pathwayCell deathERK inhibitorDNA damageTumor cell deathFitness barriersCell subclonesNew therapeutic approachesInhibitor withdrawalResistant clonesTherapeutic approachesTriple combinationMEKSignalingClonesSubclonesFitnessPathwayPatients
2011
NFBD1/MDC1 Regulates Cav1 and Cav2 Independently of DNA Damage and p53
Wilson KA, Colavito SA, Schulz V, Wakefield PH, Sessa W, Tuck D, Stern DF. NFBD1/MDC1 Regulates Cav1 and Cav2 Independently of DNA Damage and p53. Molecular Cancer Research 2011, 9: 766-781. PMID: 21551225, PMCID: PMC3901581, DOI: 10.1158/1541-7786.mcr-10-0317.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAtaxia Telangiectasia Mutated ProteinsCaveolin 1Caveolin 2Cell AdhesionCell Cycle ProteinsCell Line, TumorCells, CulturedChromatinDNA DamageDNA RepairDNA-Binding ProteinsFibroblastsGene Knockdown TechniquesHistonesHumansMiceNuclear ProteinsProtein Serine-Threonine KinasesRNA, MessengerSignal TransductionTrans-ActivatorsTranscription, GeneticTumor Suppressor Protein p53Tumor Suppressor ProteinsConceptsDNA damage checkpoint signalingNFBD1 knockdownDNA damageNFBD1/MDC1Focal adhesion signalingDNA repair factorsDNA damage responseP53-mediated transcriptionAdhesion signalingCheckpoint signalingRepair factorsResponsive transcriptionDamage responseMitogenic signalingNFBD1DNA repairNovel functionTransactivation activityGene pathwaysAtaxia telangiectasiaMicroarray analysisSimilar phenotypeERK phosphorylationGenesTranscription
2010
Interactions of ErbB4 and Kap1 Connect the Growth Factor and DNA Damage Response Pathways
Gilmore-Hebert M, Ramabhadran R, Stern DF. Interactions of ErbB4 and Kap1 Connect the Growth Factor and DNA Damage Response Pathways. Molecular Cancer Research 2010, 8: 1388-1398. PMID: 20858735, PMCID: PMC3901583, DOI: 10.1158/1541-7786.mcr-10-0042.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorChlorocebus aethiopsCOS CellsDNA DamageDown-RegulationErbB ReceptorsGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHumansIntercellular Signaling Peptides and ProteinsProtein BindingReceptor, ErbB-4Repressor ProteinsSignal TransductionSilencer Elements, TranscriptionalSubstrate SpecificityTripartite Motif-Containing Protein 28ConceptsIntracellular domainKinase activityDNA damage response pathwayDamage response pathwayDNA damage responseErbB4 intracellular domainGrowth factor signalingHigh kinase activitySoluble intracellular domainExpression of genesReceptor tyrosine kinasesSuppression of MDM2Candidate interactorsDamage responseResponse pathwaysFactor signalingPlasma membraneMultiple isoformsErbB4 kinase activityTyrosine kinaseDNA damageRole of ErbB4Protein 1KAP1Conjoint regulation
2008
Regulation of the Rad53 protein kinase in signal amplification by oligomer assembly and disassembly
Jia-Lin Ma N, Stern DF. Regulation of the Rad53 protein kinase in signal amplification by oligomer assembly and disassembly. Cell Cycle 2008, 7: 808-817. PMID: 18239457, DOI: 10.4161/cc.7.6.5595.Peer-Reviewed Original ResearchConceptsRad53 activationDNA damageOligomer assemblyRad53 kinase activityRad53 protein kinaseAbsence of Mec1DNA damage responseSignal transduction processesMammalian Chk2Autophosphorylation activityGenetic requirementsCheckpoint responseChk2 activationDamage responseEffector kinaseProtein kinaseKinase activityRad53Forms oligomersTransduction processesSCD domainsInduced oligomerizationOligomer formationOligomerizationChk2
2005
Activation of the Checkpoint Kinase Rad53 by the Phosphatidyl Inositol Kinase-like Kinase Mec1*
Ma JL, Lee SJ, Duong JK, Stern DF. Activation of the Checkpoint Kinase Rad53 by the Phosphatidyl Inositol Kinase-like Kinase Mec1*. Journal Of Biological Chemistry 2005, 281: 3954-3963. PMID: 16365046, DOI: 10.1074/jbc.m507508200.Peer-Reviewed Original ResearchConceptsPhosphorylation-dependent mechanismDNA damageKinase activityDNA replication checkpoint pathwayRad53 kinase activityCheckpoint kinase Rad53Essential protein kinaseReplication checkpoint pathwayActivation of Rad53Protein kinase activityMammalian Chk2Rad53 phosphorylationRad53 activationRad53Protein kinaseDownstream responsesCheckpoint pathwayOrthologsAutophosphorylationKinasePhosphorylationIntermolecular mechanismActivationPIKKsComplexesDNA Damage Regulates Chk2 Association with Chromatin*
Li J, Stern DF. DNA Damage Regulates Chk2 Association with Chromatin*. Journal Of Biological Chemistry 2005, 280: 37948-37956. PMID: 16150728, DOI: 10.1074/jbc.m509299200.Peer-Reviewed Original ResearchConceptsChromatin-enriched fractionDNA damageATM-dependent mannerUpstream phosphatidylinositolPresence of ATPChromatin fractionationDNA repairHypophosphorylated formEffector substratesChk2Hyperphosphorylated formsChromatinCell cyclePhosphorylated formCluster domainDiverse responsesArtificial inductionSoluble substratesCritical mediatorSmall poolSoluble fractionCdc25APhosphatidylinositolKinaseTransmit signalThe Plk1 Polo Box Domain Mediates a Cell Cycle and DNA Damage Regulated Interaction with Chk2
Tsvetkov LM, Tsekova RT, Xu X, Stern DF. The Plk1 Polo Box Domain Mediates a Cell Cycle and DNA Damage Regulated Interaction with Chk2. Cell Cycle 2005, 4: 602-610. PMID: 15876876, DOI: 10.4161/cc.4.4.1599.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCatalytic DomainCell CycleCell Cycle ProteinsCell DivisionCell SeparationCheckpoint Kinase 2DNA DamageDNA RepairG2 PhaseGenetic VectorsGlutathione TransferaseHeLa CellsHumansImmunoblottingImmunoprecipitationIn Vitro TechniquesMitosisPhosphorylationProtein BindingProtein KinasesProtein Serine-Threonine KinasesProtein Structure, TertiaryProto-Oncogene ProteinsSignal TransductionConceptsPlk1 polo-box domainDNA damage checkpointPolo-box domainPolo-like kinase 1Eukaryotic proteinsDamage checkpointMitotic regulationBox domainRegulated interactionPlk1 activityProtein kinaseSignaling cascadesChk2Kinase 1Tumor suppressorCell cycleDNA damageS phasePlk1M phaseMitosisMultiple processesPotential mechanismsPhosphorylatesKinaseRegulation of CHK2 by DNA-dependent Protein Kinase*
Li J, Stern DF. Regulation of CHK2 by DNA-dependent Protein Kinase*. Journal Of Biological Chemistry 2005, 280: 12041-12050. PMID: 15668230, DOI: 10.1074/jbc.m412445200.Peer-Reviewed Original ResearchMeSH KeywordsAndrostadienesAntigens, NuclearAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCells, CulturedCheckpoint Kinase 2DNADNA DamageDNA-Activated Protein KinaseDNA-Binding ProteinsEnzyme ActivationHumansKu AutoantigenNuclear ProteinsPhosphorylationProtein Serine-Threonine KinasesTumor Suppressor ProteinsWortmanninConceptsActivation of Chk2DNA-PKChk2 phosphorylationDNA damageDNA-Dependent Protein Kinase Catalytic SubunitProtein Kinase Catalytic SubunitDNA-dependent protein kinaseFunctional DNA-PKRegulation of Chk2Kinase catalytic subunitRegulation of DNAChk2 kinase activityATM-deficient cellsDiverse cellular responsesKinase inhibitor wortmanninATM-defective cellsChk2 activationExposure of cellsCatalytic subunitProtein kinaseKinase activityChk2Inhibitor wortmanninRabbit reticulocytesCellular responses
2004
Phosphorylation of Plk1 at S137 and T210 is Inhibited in Response to DNA Damage
Tsvetkov L, Stern DF. Phosphorylation of Plk1 at S137 and T210 is Inhibited in Response to DNA Damage. Cell Cycle 2004, 4: 166-171. PMID: 15611664, DOI: 10.4161/cc.4.1.1348.Peer-Reviewed Original ResearchMeSH KeywordsAtaxia Telangiectasia Mutated ProteinsCaffeineCDC2 Protein KinaseCdc25 PhosphatasesCell Cycle ProteinsCell DivisionCell Line, TumorCheckpoint Kinase 1Checkpoint Kinase 2Cyclin BDNA DamageDNA-Binding ProteinsDoxorubicinEnzyme ActivationG2 PhaseHumansMitosisNocodazolePhosphorylationProtein KinasesProtein Serine-Threonine KinasesProto-Oncogene ProteinsSerineSignal TransductionStaurosporineThreonineTumor Suppressor ProteinsConceptsDNA damage checkpointThreonine 210Damage checkpointPlk1 phosphorylationDNA damageCdc2/cyclin B kinaseATR-dependent checkpoint pathwayChk2 protein kinaseDNA damage-induced inhibitionATM/ATRCyclin B kinasePolo-like kinase 1Phosphorylation of PLK1Activation of Cdc25CNuclear importPhosphopeptide mappingMitotic entryActivation loopPhosphorylation sitesVivo phosphorylationPlk1 activityKinase domainProtein kinasePrevents phosphorylationActive mutantA Ddc2-Rad53 Fusion Protein Can Bypass the Requirements for RAD9 and MRC1 in Rad53 Activation
Lee SJ, Duong JK, Stern DF. A Ddc2-Rad53 Fusion Protein Can Bypass the Requirements for RAD9 and MRC1 in Rad53 Activation. Molecular Biology Of The Cell 2004, 15: 5443-5455. PMID: 15456903, PMCID: PMC532024, DOI: 10.1091/mbc.e04-07-0608.Peer-Reviewed Original ResearchConceptsDNA damageDNA damage checkpoint pathwayFusion proteinDamage checkpoint pathwayRad53p activationRad53 activationMethyl methaneCheckpoint pathwaySignaling systemCell survivalMediator requirementMec1pEssential roleProteinCellsActivationExpressionRad53pRad9pDdc2Rad9Mrc1pMinimal requirementsMrc1OligomerizationEstablishment of a Cell-Free System to Study the Activation of Chk2
Xu X, Stern DF. Establishment of a Cell-Free System to Study the Activation of Chk2. Methods In Molecular Biology 2004, 280: 165-174. PMID: 15187252, DOI: 10.1385/1-59259-788-2:165.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell-Free SystemCheckpoint Kinase 2DNA DamageDNA-Binding ProteinsGenetic VectorsHumansImmunoblottingPlasmidsPrecipitin TestsProtein BiosynthesisProtein Serine-Threonine KinasesRabbitsReticulocytesTranscription, GeneticTriticumTumor Suppressor ProteinsConceptsActivation of Chk2Cell-free systemVitro transcription/translation systemTranscription/translation systemCheckpoint kinase Chk2Rabbit reticulocyte lysateWheat germ extractKinase Chk2Identification of cofactorsReticulocyte lysateChk2Germ extractDNA damageTranslation systemActivationKinaseCofactorProteinATRLysatesPathway
2003
NFBD1/MDC1 regulates ionizing radiation‐induced focus formation by DNA checkpoint signaling and repair factors
Xu X, Stern DF. NFBD1/MDC1 regulates ionizing radiation‐induced focus formation by DNA checkpoint signaling and repair factors. The FASEB Journal 2003, 17: 1842-1848. PMID: 14519663, DOI: 10.1096/fj.03-0310com.Peer-Reviewed Original ResearchConceptsNFBD1/MDC1DNA checkpointMRN complexRepair factorsIRIF formationATM/ATR substratesRadiation-induced nuclear fociRadiation-induced focus formationDNA damageBRCT domainFHA domainATR substratesNbs1 complexMre11-Rad50Nuclear fociNFBD1Repair proteinsTandem repeatsFoci formationMre11NBS1MDC1CheckpointNuclear factorBindsRad53 Phosphorylation Site Clusters Are Important for Rad53 Regulation and Signaling
Lee SJ, Schwartz MF, Duong JK, Stern DF. Rad53 Phosphorylation Site Clusters Are Important for Rad53 Regulation and Signaling. Molecular And Cellular Biology 2003, 23: 6300-6314. PMID: 12917350, PMCID: PMC180918, DOI: 10.1128/mcb.23.17.6300-6314.2003.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmino Acid SubstitutionBinding SitesCell Cycle ProteinsCheckpoint Kinase 2DNA DamageFungal ProteinsIntracellular Signaling Peptides and ProteinsMAP Kinase Kinase 1Mitogen-Activated Protein Kinase KinasesMutationPhosphorylationProtein KinasesProtein Serine-Threonine KinasesProtein Structure, TertiarySaccharomyces cerevisiae ProteinsSaccharomycetalesSchizosaccharomyces pombe ProteinsSignal TransductionConceptsDNA damage-induced interactionsPhosphorylation of Rad53Rad53 kinase activityTel1-dependent mannerEssential protein kinaseDNA damageConsensus phosphorylation sitesRad53 activationRad53 phosphorylationFHA domainPhosphorylation sitesCheckpoint functionUpstream kinaseYeast Rad53Protein kinaseRad53Kinase activityAlanine substitutionsReplication blockadeBasal interactionSubstitution mutationsImpaired interactionDun1Mec1Site clustersFHA Domain-Mediated DNA Checkpoint Regulation of Rad53
Schwartz MF, Lee SJ, Duong JK, Eminaga S, Stern DF. FHA Domain-Mediated DNA Checkpoint Regulation of Rad53. Cell Cycle 2003, 2: 381-394. PMID: 12851493, DOI: 10.4161/cc.2.4.457.Peer-Reviewed Original ResearchConceptsDNA damage checkpoint pathwayDamage checkpoint pathwayFHA domainReplication blocksCheckpoint pathwayChromatin assembly factor Asf1Phosphorylation-dependent associationDNA damageDNA replication checkpointActivation of Rad53Phosphopeptide binding domainsReplication checkpointReplicational stressDNA checkpointCheckpoint defectRad53Checkpoint regulationCatalytic domainProtein kinaseFHA1Binding domainsAsf1FHA2Persistent activationPathway
2002
Chk2 Activation and Phosphorylation-Dependent Oligomerization
Xu X, Tsvetkov LM, Stern DF. Chk2 Activation and Phosphorylation-Dependent Oligomerization. Molecular And Cellular Biology 2002, 22: 4419-4432. PMID: 12024051, PMCID: PMC133858, DOI: 10.1128/mcb.22.12.4419-4432.2002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxia Telangiectasia Mutated ProteinsBinding SitesCell Cycle ProteinsCell-Free SystemCells, CulturedCheckpoint Kinase 2DNA DamageDNA-Binding ProteinsEnzyme ActivationFibroblastsGenes, Tumor SuppressorHumansMutationPhosphorylationProtein KinasesProtein Serine-Threonine KinasesProtein Structure, TertiaryRabbitsRadiation, IonizingRecombinant ProteinsSignal TransductionTumor Suppressor ProteinsConceptsSQ/TQ cluster domainsChk2 activationDNA damageDNA damage checkpoint pathwaySerine/threonine kinaseAutophosphorylation of Chk2Phosphorylation-dependent oligomerizationDamage checkpoint pathwayKinase catalytic domainForkhead-associated (FHA) domainWortmannin-sensitive kinaseChk2 kinase activityLimited DNA damageAmino acid substitutionsCell-free systemEukaryotic proteinsFHA domainActive Chk2Threonine kinaseCheckpoint functionCatalytic domainOligomeric complexesCheckpoint pathwayKinase activityChk2
1998
Rad53 FHA Domain Associated with Phosphorylated Rad9 in the DNA Damage Checkpoint
Sun Z, Hsiao J, Fay D, Stern D. Rad53 FHA Domain Associated with Phosphorylated Rad9 in the DNA Damage Checkpoint. Science 1998, 281: 272-274. PMID: 9657725, DOI: 10.1126/science.281.5374.272.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell Cycle ProteinsCheckpoint Kinase 2DNA DamageDNA ReplicationFungal ProteinsG2 PhaseHydroxyureaMethyl MethanesulfonateMitosisMutationOligopeptidesPeptidesPhosphorylationProtein KinasesProtein Serine-Threonine KinasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTranscription, GeneticConceptsRad53 phosphorylationRad53 protein kinaseDNA damage signalsDNA damage checkpointProtein-binding domainsCell cycle phase arrestRNR3 transcriptionRad9 proteinFHA domainDamage checkpointG2/M cell cycle phase arrestCell divisionProtein kinaseSaccharomyces cerevisiaeDamage signalsRad9DNA damageRad53Phase arrestPhosphorylationCheckpointDomainCerevisiaeTranscriptionKinase
1997
A role for DNA primase in coupling DNA replication to DNA damage response
Marini F, Pellicioli A, Paciotti V, Lucchini G, Plevani P, Stern D, Foiani M. A role for DNA primase in coupling DNA replication to DNA damage response. The EMBO Journal 1997, 16: 639-650. PMID: 9034345, PMCID: PMC1169666, DOI: 10.1093/emboj/16.3.639.Peer-Reviewed Original ResearchMeSH KeywordsBlotting, WesternCell CycleCell Cycle ProteinsCheckpoint Kinase 2DNADNA DamageDNA PrimaseDNA ReplicationEnzyme StabilityFlow CytometryFungal ProteinsGene Expression Regulation, FungalGenes, FungalInterphaseMethyl MethanesulfonateMitosisModels, BiologicalMutagenesis, Site-DirectedMutagensMutationPhosphorylationProtein KinasesProtein Serine-Threonine KinasesRNA NucleotidyltransferasesS PhaseSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTemperatureUltraviolet RaysConceptsDNA damage responseDNA replicationDamage responseDNA damageDNA primaseS-phase progressionSignal transduction pathwaysDNA-damaging agentsCell cycle progressionCell cycle delayG1-S transitionRad53p phosphorylationTransduction pathwaysCheckpoint pathwayCycle progressionCycle delayPhase progressionEarly stepsEssential rolePrimaseReplicationPathwayMitosisPhosphorylationOverexpression
1995
ScSpk1 Spk1 (S. cerevisiae)
Zheng P, Fay D, Stern D. ScSpk1 Spk1 (S. cerevisiae). 1995, 126-127. DOI: 10.1016/b978-012324719-3/50028-5.Peer-Reviewed Original ResearchKinase domainProtein kinaseMluI cell cycle boxS-phase-specific genesS phase-specific expressionPhase-specific genesPhase-specific expressionTyr kinase activitySer/ThrSpecific protein kinasesProtein tyrosine kinasesTranscriptional regulationMutant cellsNuclear proteinsNuclear localizationKinase activitySPK1DNA damageKinaseDNA synthesisProteinRepair synthesisGenesLatter activityImportant role