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 microscopyMidbodyRad9 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
2010
Deciphering 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
2005
Global 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 technologyTargetPhosphoproteomics for oncology discovery and treatment
Stern DF. Phosphoproteomics for oncology discovery and treatment. Expert Opinion On Therapeutic Targets 2005, 9: 851-860. PMID: 16083347, DOI: 10.1517/14728222.9.4.851.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsGene Expression ProfilingHumansNeoplasmsPhosphoproteinsProtein KinasesProteomicsConceptsPhosphoproteomic analysisProtein phosphorylationReversible protein phosphorylationSignal transduction pathwaysCellular regulationProtein kinaseTransduction pathwaysHuman cancersDevelopment of drugsPathwayPhosphorylationGood targetImportant insightsCancer therapyCancer drugsPhosphoproteomicsCellsIndividual tumorsPowerful toolKinaseRegulationIntermediary levelDiscoveryTargetIdentificationThe 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 mechanismsPhosphorylatesKinaseInteraction 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 mutant
2003
Rad53 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 clusters
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
Mutations in SPK1/RAD53 that specifically abolish checkpoint but not growth-related functions
Fay DS, Sun Z, Stern D. Mutations in SPK1/RAD53 that specifically abolish checkpoint but not growth-related functions. Current Genetics 1997, 31: 97-105. PMID: 9021124, DOI: 10.1007/s002940050181.Peer-Reviewed Original ResearchMeSH KeywordsAllelesCell Cycle ProteinsCheckpoint Kinase 2Cloning, MolecularElectrophoresis, Polyacrylamide GelGene Expression Regulation, EnzymologicGene Expression Regulation, FungalMutagenesisPlasmidsProtein KinasesProtein Serine-Threonine KinasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence DeletionTransformation, GeneticConceptsCheckpoint functionKinase domainKinase activityEssential protein kinaseWild-type levelsGrowth-related functionsCheckpoint arrestProtein kinaseDeletional analysisN-terminusSPK1Cell cycleMutant allelesGrowth activityMutationsRad53Normal rateSaccharomycesMultiple stagesKinaseDomainCheckpointActivityAllelesRegulationA 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
1996
Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways.
Sun Z, Fay DS, Marini F, Foiani M, Stern DF. Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways. Genes & Development 1996, 10: 395-406. PMID: 8600024, DOI: 10.1101/gad.10.4.395.Peer-Reviewed Original ResearchMeSH KeywordsAlkaline PhosphataseCell CycleCell Cycle ProteinsCell DivisionCheckpoint Kinase 2DNA DamageDNA ReplicationDNA, FungalFungal ProteinsGene Expression Regulation, FungalGenes, FungalHydroxyureaImmunoblottingIntracellular Signaling Peptides and ProteinsMethyl MethanesulfonateMutagenesisPhosphorylationPrecipitin TestsProtein KinasesProtein Serine-Threonine KinasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSignal TransductionTemperatureConceptsProtein kinaseCheckpoint pathwayEssential protein kinaseDamage checkpoint pathwayDamage-induced phosphorylationKinase-defective formG1/S boundarySignal transduction pathwaysRegulation of phosphorylationTreatment of cellsCheckpoint functionCdc mutantsDNA replicationProtein phosphorylationUpstream kinaseCheckpoint arrestRegulated phosphorylationTransduction pathwaysKinase activityCell cyclePhosphorylationS boundaryDamage DNACycle arrestKinase
1993
SPK1 is an essential S-phase-specific gene of Saccharomyces cerevisiae that encodes a nuclear serine/threonine/tyrosine kinase.
Zheng P, Fay DS, Burton J, Xiao H, Pinkham JL, Stern DF. SPK1 is an essential S-phase-specific gene of Saccharomyces cerevisiae that encodes a nuclear serine/threonine/tyrosine kinase. Molecular And Cellular Biology 1993, 13: 5829-5842. PMID: 8355715, PMCID: PMC360328, DOI: 10.1128/mcb.13.9.5829.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceCell Cycle ProteinsCheckpoint Kinase 2Chromosome MappingDNA RepairFungal ProteinsGene ExpressionGene Expression Regulation, FungalGenes, FungalMolecular Sequence DataMutagenesis, InsertionalNuclear ProteinsOligodeoxyribonucleotidesPromoter Regions, GeneticProtein KinasesProtein Serine-Threonine KinasesRestriction MappingRNA, MessengerS PhaseSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentSubstrate SpecificityConceptsSerine/threonine/tyrosine kinasesS-phase-specific transcriptionCell cycle-dependent transcriptionS-phase-specific genesDual-specificity protein kinaseImmune complex kinase assayTyr kinase activityTyrosine protein kinaseDNA synthesisExcision repair genesBudded cellsCEN plasmidGenomic libraryPositive regulatorProtein-SerKinase assaysProtein kinaseNuclear localizationNucleotide sequenceBox elementKinase activityGenetic techniquesSPK1Tyrosine kinaseUpstream region
1991
Spk1, a new kinase from Saccharomyces cerevisiae, phosphorylates proteins on serine, threonine, and tyrosine.
Stern DF, Zheng P, Beidler DR, Zerillo C. Spk1, a new kinase from Saccharomyces cerevisiae, phosphorylates proteins on serine, threonine, and tyrosine. Molecular And Cellular Biology 1991, 11: 987-1001. PMID: 1899289, PMCID: PMC359764, DOI: 10.1128/mcb.11.2.987.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBinding SitesCell Cycle ProteinsCheckpoint Kinase 2Cloning, MolecularEscherichia coliFungal ProteinsGene LibraryGenes, FungalImmunoblottingMolecular Sequence DataProtein KinasesProtein Serine-Threonine KinasesProtein-Tyrosine KinasesRecombinant ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Homology, Nucleic AcidSerineSubstrate SpecificityThreonineTyrosineConceptsSerine/threonine kinaseProtein kinaseFusion proteinThreonine kinaseTyrosine phosphorylationGlutathione S-transferase fusion proteinCyclic AMP-dependent protein kinaseAMP-dependent protein kinaseSerine protein kinaseSerine/threonineCalmodulin-dependent protein kinase IICalcium/calmodulin-dependent protein kinase IITyrosine protein kinaseOpen reading frameProtein kinase IILambda gt11 libraryPutative kinaseNew kinasesThreonine phosphorylationCatalytic subunitSaccharomyces cerevisiaeBacterial proteinsReading frameAntiphosphotyrosine antibodyKinase II