Featured Publications
Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma
Tworkoski K, Singhal G, Szpakowski S, Zito CI, Bacchiocchi A, Muthusamy V, Bosenberg M, Krauthammer M, Halaban R, Stern DF. Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma. Molecular Cancer Research 2011, 9: 801-812. PMID: 21521745, PMCID: PMC3117976, DOI: 10.1158/1541-7786.mcr-10-0512.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCell Line, TumorCell MovementCell ProliferationErbB ReceptorsGene Expression Regulation, NeoplasticGene Knockdown TechniquesHEK293 CellsHumansInfant, NewbornMelanocytesMelanomaPhosphoproteinsPhosphorylationProteomicsReceptor Protein-Tyrosine KinasesReceptor, IGF Type 2RNA, Small InterferingSignal TransductionSkin NeoplasmsSTAT3 Transcription FactorConceptsTherapeutic targetReceptor tyrosine kinasesMelanoma cellsPotential therapeutic targetIdentifies potential therapeutic targetsActive receptor tyrosine kinasesTyrosine kinaseMelanoma cell migrationReceptor expressionBreast cancerAxl knockdownAutocrine circuitTherapeutic interventionsCancer subtypesReceptor tyrosine kinase activationTyrosine kinase activationNovel targetActivated receptorsAxlRNA knockdownMelanomaCell migrationHER3KnockdownIGF1RMicrocephalin 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 diseaseMDC1PtcbGenesNFBD1/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 FactorsActivation state-specific monoclonal antibody detects tyrosine phosphorylated p185neu/erbB-2 in a subset of human breast tumors overexpressing this receptor.
DiGiovanna MP, Stern DF. Activation state-specific monoclonal antibody detects tyrosine phosphorylated p185neu/erbB-2 in a subset of human breast tumors overexpressing this receptor. Cancer Research 1995, 55: 1946-55. PMID: 7728765.Peer-Reviewed Original ResearchConceptsHuman breast tumorsBreast tumorsPrimary human breast tumorsPoor patient prognosisSubset of tumorsEpidermal growth factor receptorGrowth factor receptorPatient prognosisImmunohistochemical stainingNeu/ErbBTumor samplesTumorsMonoclonal antibodiesHuman tumorsFactor receptorRelated receptorsReceptorsP185Polyclonal antibodiesAntibodiesErbBRelated epidermal growth factor receptorSubsetTyrosine phosphoproteinsPrognosisThe Cellular Response to Neuregulins Is Governed by Complex Interactions of the erbB Receptor Family
Riese D, van Raaij T, Plowman G, Andrews G, Stern D. The Cellular Response to Neuregulins Is Governed by Complex Interactions of the erbB Receptor Family. Molecular And Cellular Biology 1995, 15: 5770-5776. PMID: 7565730, PMCID: PMC230829, DOI: 10.1128/mcb.15.10.5770.Peer-Reviewed Original ResearchConceptsReceptor familyEpidermal growth factor receptor tyrosine kinase familyErbB family receptorsErbB receptor familyReceptor tyrosine kinase familyReceptor tyrosine phosphorylationPeptide agonistsFamily receptorsTyrosine kinase familyHuman cancersReceptor interactionEpidermal growth factor homology domainsCell linesCell survivalReceptorsNeuregulinCellular responsesTyrosine phosphorylationEGF‐stimulated tyrosine phosphorylation of p185neu: a potential model for receptor interactions.
Stern DF, Kamps MP. EGF‐stimulated tyrosine phosphorylation of p185neu: a potential model for receptor interactions. The EMBO Journal 1988, 7: 995-1001. PMID: 3261240, PMCID: PMC454426, DOI: 10.1002/j.1460-2075.1988.tb02906.x.Peer-Reviewed Original ResearchConceptsEGF-stimulated tyrosine phosphorylationTyrosine phosphorylationEGF receptorKinase activityReceptor-like proteinEGF receptor kinaseIntrinsic kinase activityRat-1 cellsTyrosine kinase activityEpidermal growth factor receptorReceptor kinaseGrowth factor receptorIncubation of cellsPhosphorylationEGFNeu/Factor receptorReceptor interactionSimilar kineticsGrowth factorP185ProteinP185neuReceptorsCells
2013
Comparison of HER2 and Phospho-HER2 Expression between Biopsy and Resected Breast Cancer Specimens Using a Quantitative Assessment Method
Bai Y, Cheng H, Bordeaux J, Neumeister V, Kumar S, Rimm DL, Stern DF. Comparison of HER2 and Phospho-HER2 Expression between Biopsy and Resected Breast Cancer Specimens Using a Quantitative Assessment Method. PLOS ONE 2013, 8: e79901. PMID: 24278211, PMCID: PMC3836903, DOI: 10.1371/journal.pone.0079901.Peer-Reviewed Original ResearchConceptsCore needle biopsyBreast cancer casesResection specimensCancer casesHER2/neu overexpressionPrediction of responsePre-analytic variablesNeu overexpressionTumor resectionNeedle biopsyBreast cancerHER2 immunoreactivityRetrospective collectionHER2Drug trastuzumabClinical implicationsHER2 proteinQuantitative immunofluorescenceResectionPHER2Good responseFurther studiesBiopsyTrastuzumabImmunoreactivityEGF Receptor Activates MET through MAPK to Enhance Non–Small Cell Lung Carcinoma Invasion and Brain Metastasis
Breindel JL, Haskins JW, Cowell EP, Zhao M, Nguyen DX, Stern DF. EGF Receptor Activates MET through MAPK to Enhance Non–Small Cell Lung Carcinoma Invasion and Brain Metastasis. Cancer Research 2013, 73: 5053-5065. PMID: 23794705, PMCID: PMC3745527, DOI: 10.1158/0008-5472.can-12-3775.Peer-Reviewed Original ResearchConceptsNon-small cell lung carcinomaMitogen-activated protein kinaseBrain metastasesEGFR-METMET activationMutant EGFRCell lung carcinomaEffect of MetSMET kinase inhibitorEGF receptorErbB family membersMET amplificationLung carcinomaDrug treatmentTherapeutic targetEGFRMet levelsDrug resistanceCell subpopulationsCarcinoma invasionKinase inhibitorsMET phosphorylationProtein levelsMetSContinued investigationMERTK controls melanoma cell migration and survival and differentially regulates cell behavior relative to AXL
Tworkoski KA, Platt JT, Bacchiocchi A, Bosenberg M, Boggon TJ, Stern DF. MERTK controls melanoma cell migration and survival and differentially regulates cell behavior relative to AXL. Pigment Cell & Melanoma Research 2013, 26: 527-541. PMID: 23617806, PMCID: PMC3918898, DOI: 10.1111/pcmr.12110.Peer-Reviewed Original ResearchMeSH KeywordsAxl Receptor Tyrosine KinaseCdc42 GTP-Binding ProteinCell Line, TumorCell MovementCell ProliferationCell SurvivalC-Mer Tyrosine KinaseCytophotometryGene Expression ProfilingGene Expression Regulation, NeoplasticHEK293 CellsHumansMelanomaNeoplasm MetastasisOligonucleotide Array Sequence AnalysisPhosphorylationProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSignal TransductionSkin NeoplasmsConceptsCell migrationCell behaviorMelanoma cellsAkt-dependent mannerShRNA-mediated knockdownDifferential cell behaviorDifferent transcriptional signaturesReceptor tyrosine kinase AXLMelanoma cell migrationMelanoma cell proliferationKinase domainTyrosine kinase AXLCell motilityTranscriptional signatureCell survivalColony formationCell proliferationOverexpression of AxlPossible therapeutic targetMelanoma pathogenesisNovel mutationsMerTKAxlTherapeutic targetMutations
2010
Centrosomal Chk2 in DNA damage responses and cell cycle progession
Golan A, Pick E, Tsvetkov L, Nadler Y, Kluger H, Stern DF. Centrosomal Chk2 in DNA damage responses and cell cycle progession. Cell Cycle 2010, 9: 2647-2656. PMID: 20581449, PMCID: PMC3233491, DOI: 10.4161/cc.9.13.12121.Peer-Reviewed Original ResearchDeciphering Protein Kinase Specificity Through Large-Scale Analysis of Yeast Phosphorylation Site Motifs
Mok J, Kim PM, Lam HY, Piccirillo S, Zhou X, Jeschke GR, Sheridan DL, Parker SA, Desai V, Jwa M, Cameroni E, Niu H, Good M, Remenyi A, Nianhan J, Sheu YJ, Sassi HE, Sopko R, Chan CS, De Virgilio C, Hollingsworth NM, Lim WA, Stern DF, Stillman B, Andrews BJ, Gerstein MB, Snyder M, Turk BE. Deciphering Protein Kinase Specificity Through Large-Scale Analysis of Yeast Phosphorylation Site Motifs. Science Signaling 2010, 3: ra12. PMID: 20159853, PMCID: PMC2846625, DOI: 10.1126/scisignal.2000482.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceMolecular Sequence DataPhosphorylationProtein KinasesSaccharomyces cerevisiaeSubstrate SpecificityConceptsPhosphorylation site motifsSite motifShort linear sequence motifsKinase substrate recognitionKinase-substrate relationshipsProtein kinase specificityKinase catalytic domainLinear sequence motifsPrediction of thousandsCMGC groupKinase specificityPhosphorylation targetsKinase substrateYeast proteomeSequence motifsSubstrate recognitionKinase familyProtein substratesCatalytic domainProtein kinaseLarge-scale analysisPrimary sequenceCandidate substratesComputational scanningKinase
2009
BRCTing Up Is Hard to Do
Stern DF. BRCTing Up Is Hard to Do. Molecular Cell 2009, 33: 137-138. PMID: 19187753, DOI: 10.1016/j.molcel.2009.01.005.Peer-Reviewed Original Research
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 foreskinInfluence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B
DiGiovanna MP, Stern DF, Edgerton S, Broadwater G, Dressler LG, Budman DR, Henderson IC, Norton L, Liu ET, Muss HB, Berry DA, Hayes DF, Thor AD. Influence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B. Journal Of Clinical Oncology 2008, 26: 2364-2372. PMID: 18390970, PMCID: PMC6589994, DOI: 10.1200/jco.2007.13.6580.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDisease-Free SurvivalDose-Response Relationship, DrugDoxorubicinEnzyme ActivationFemaleFluorouracilGene DosageHumansImmunohistochemistryIn Situ Hybridization, FluorescenceLymphatic MetastasisNeoplasm StagingPhosphorylationReceptor, ErbB-2ConceptsLeukemia Group BAdjuvant cyclophosphamideErbB-2Breast cancerGroup BAnthracycline-based adjuvant chemotherapyNode-positive breast cancerAdverse prognostic factorSpecific chemotherapeutic agentsErbB-2 overexpressionActivation stateTumor tissue sectionsAdjuvant chemotherapyCAF doseCALGB 8541Fluorouracil chemotherapyPrognostic factorsAssessable casesFavorable outcomePatientsChemotherapeutic agentsStage IICancerDoseTissue sectionsRegulation 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 mechanismActivationPIKKsComplexesGlobal analysis of protein phosphorylation in yeast
Ptacek J, Devgan G, Michaud G, Zhu H, Zhu X, Fasolo J, Guo H, Jona G, Breitkreutz A, Sopko R, McCartney RR, Schmidt MC, Rachidi N, Lee SJ, Mah AS, Meng L, Stark MJ, Stern DF, De Virgilio C, Tyers M, Andrews B, Gerstein M, Schweitzer B, Predki PF, Snyder M. Global analysis of protein phosphorylation in yeast. Nature 2005, 438: 679-684. PMID: 16319894, DOI: 10.1038/nature04187.Peer-Reviewed Original ResearchConceptsProtein phosphorylationBasic cellular processesGlobal phosphorylation networksFirst-generation mapYeast kinasesPhosphorylation networksYeast proteinsCellular processesPhosphorylationKinaseYeastSearchable formatGlobal analysisProteinPrime targetEukaryotesNew resourcesProteomicsOrganismsRegulationPathwayChip technologyTargetDNA 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 mechanismsPhosphorylatesKinase