Featured Publications
Microcephalin Is a DNA Damage Response Protein Involved in Regulation of CHK1 and BRCA1 * ♦
Xu X, Lee J, Stern DF. Microcephalin Is a DNA Damage Response Protein Involved in Regulation of CHK1 and BRCA1 * ♦. Journal Of Biological Chemistry 2004, 279: 34091-34094. PMID: 15220350, DOI: 10.1074/jbc.c400139200.Peer-Reviewed Original ResearchMeSH KeywordsBlotting, NorthernBlotting, WesternBRCA1 ProteinCell CycleCell Cycle ProteinsCell LineCheckpoint Kinase 1Cytoskeletal ProteinsDNADNA DamageDown-RegulationG2 PhaseGene Expression RegulationGene Expression Regulation, NeoplasticHistonesHumansMicroscopy, FluorescenceMitosisNerve Tissue ProteinsPhosphorylationPlasmidsPrecipitin TestsProtein KinasesProtein Structure, TertiaryRadiation, IonizingRNA, MessengerRNA, Small InterferingConceptsDNA damage-induced cellular responsesDNA damage response proteinsCellular responsesDamage response proteinsNFBD1/MDC1Regulation of BRCA1Regulation of Chk1Radiation-induced fociEndogenous BRCA1BRCT domainFirst geneResponse proteinsTranscript levelsMCPH1Primary microcephalyProteinMicrocephalinChk1Autosomal recessive diseaseBRCA1RegulationRecessive diseaseMDC1PtcbGenesPolo-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 stainingRad9 Phosphorylation Sites Couple Rad53 to the Saccharomyces cerevisiae DNA Damage Checkpoint
Schwartz MF, Duong JK, Sun Z, Morrow JS, Pradhan D, Stern DF. Rad9 Phosphorylation Sites Couple Rad53 to the Saccharomyces cerevisiae DNA Damage Checkpoint. Molecular Cell 2002, 9: 1055-1065. PMID: 12049741, DOI: 10.1016/s1097-2765(02)00532-4.Peer-Reviewed Original ResearchBinding SitesCell Cycle ProteinsCheckpoint Kinase 1Checkpoint Kinase 2DNA DamageForkhead Transcription FactorsMutationNuclear ProteinsPhosphorylationProtein KinasesProtein Serine-Threonine KinasesProtein Structure, TertiarySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTranscription Factors
2014
Neuregulin 1–activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration
Haskins JW, Nguyen DX, Stern DF. Neuregulin 1–activated ERBB4 interacts with YAP to induce Hippo pathway target genes and promote cell migration. Science Signaling 2014, 7: ra116. PMID: 25492965, PMCID: PMC4648367, DOI: 10.1126/scisignal.2005770.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsCell Cycle ProteinsCell Line, TumorCell MovementConnective Tissue Growth FactorErlotinib HydrochlorideFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesHippo Signaling PathwayHumansLapatinibMechanotransduction, CellularNeuregulin-1Nuclear ProteinsProtein Kinase InhibitorsProtein Serine-Threonine KinasesQuinazolinesReceptor, ErbB-4Transcription FactorsConceptsIntracellular domainHippo pathway target genesHippo tumor suppressor pathwayCell migrationTranscriptional coactivator YAPCultured mammary epithelial cellsTumor suppressor pathwayPathway target genesSoluble intracellular domainExpression of genesEpidermal growth factor receptor familyMammary epithelial cellsGrowth factor receptor familyNuclear functionsIntramembrane proteolysisCoactivator YAPFactor receptor familyGrowth factor receptorTarget genesYAP activityNeuregulin-1Receptor tyrosine kinase ErbB4Receptor familyMechanosensory pathwayBreast cancer cell lines
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
2008
NFBD1/MDC1, 53BP1 and BRCA1 have both redundant and unique roles in the ATM pathway
Wilson KA, Stern DF. NFBD1/MDC1, 53BP1 and BRCA1 have both redundant and unique roles in the ATM pathway. Cell Cycle 2008, 7: 3584-3594. PMID: 19001859, PMCID: PMC2763172, DOI: 10.4161/cc.7.22.7102.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAtaxia Telangiectasia Mutated ProteinsBRCA1 ProteinCell Cycle ProteinsCell LineCheckpoint Kinase 2DNA-Binding ProteinsFibroblastsHumansIntracellular Signaling Peptides and ProteinsNuclear ProteinsPhosphorylationProtein Serine-Threonine KinasesRadiation, IonizingRNA, Small InterferingTrans-ActivatorsTumor Suppressor p53-Binding Protein 1Tumor Suppressor ProteinsConceptsNFBD1/MDC1DNA damage checkpoint proteinsRadiation-induced phosphorylationATM-Chk2 pathwayNormal genetic backgroundBRCT domainCheckpoint responseRedundant functionsPrimary human cellsRedundant rolesATM pathwayNFBD1Checkpoint proteinsMouse cellsHuman cellsGenetic backgroundMDC1Cancer cellsLocalization eventsPhosphorylationBRCA1Unique rolePathwayCellsHuman foreskinRegulation 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 responsesInteraction of Chromatin-associated Plk1 and Mcm7*
Tsvetkov L, Stern DF. Interaction of Chromatin-associated Plk1 and Mcm7*. Journal Of Biological Chemistry 2005, 280: 11943-11947. PMID: 15654075, DOI: 10.1074/jbc.m413514200.Peer-Reviewed Original ResearchMeSH KeywordsCell Cycle ProteinsCells, CulturedChromatinDNA DamageDNA ReplicationDNA-Binding ProteinsHumansImmunoprecipitationMinichromosome Maintenance Complex Component 3Minichromosome Maintenance Complex Component 7MitosisNuclear ProteinsPhosphorylationProtein KinasesProtein Serine-Threonine KinasesProto-Oncogene ProteinsTranscription FactorsConceptsPolo-box domainEndogenous Plk1Mcm2-7 protein complexPBD of Plk1DNA damage checkpointMultifunctional protein kinaseInteraction of chromatinFull-length Plk1Soluble chromatin fractionMinichromosome maintenance proteinsChromosome segregationMitotic exitDamage checkpointPlk1 interactsMitotic structuresProtein complexesMitotic entryDNA replicationChromatin fractionProtein kinaseMitotic eventsMaintenance proteinsCell cyclePlk1MCM7
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