Featured Publications
Genotype-Selective Combination Therapies for Melanoma Identified by High-Throughput Drug Screening
Held MA, Langdon CG, Platt JT, Graham-Steed T, Liu Z, Chakraborty A, Bacchiocchi A, Koo A, Haskins JW, Bosenberg MW, Stern DF. Genotype-Selective Combination Therapies for Melanoma Identified by High-Throughput Drug Screening. Cancer Discovery 2013, 3: 52-67. PMID: 23239741, PMCID: PMC3546137, DOI: 10.1158/2159-8290.cd-12-0408.Peer-Reviewed Original ResearchConceptsMutant BRAF melanomaCyclin-dependent kinase inhibitorBRAF melanomaSmall molecule inhibitorsHigh-throughput drug screeningDrug screeningEGF receptorCombination therapyDrug combinationsMelanoma culturesContext of genotypePairwise combinationsResistance phenotypeCombinatorial drug screeningUnique treatment regimensCombination of statinsVivo xenograftsKinase inhibitorsMutant BRAFMutationsEfficacious drug combinationsPartial responseTreatment regimensRAS mutationsBRAF mutationsErbB2 is required for ductal morphogenesis of the mammary gland
Jackson-Fisher AJ, Bellinger G, Ramabhadran R, Morris JK, Lee KF, Stern DF. ErbB2 is required for ductal morphogenesis of the mammary gland. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 17138-17143. PMID: 15569931, PMCID: PMC535384, DOI: 10.1073/pnas.0407057101.Peer-Reviewed Original ResearchConceptsKinase geneNormal mouse mammary gland developmentReceptor kinase geneMammary budMouse mammary gland developmentReceptor tyrosine kinase geneTyrosine kinase geneMammary gland developmentMammary glandImportant normal functionsFunctions of ErbB2Gland developmentDuctal morphogenesisEpithelial treeLobuloalveolar developmentTerminal end budsLuminal spaceBudsGenesErbB2End budsHuman breast cancerAggressive phenotypeBreast cancerNormal functionActivation of Neu (ErbB-2) Mediated by Disulfide Bond-Induced Dimerization Reveals a Receptor Tyrosine Kinase Dimer Interface
Burke C, Stern D. Activation of Neu (ErbB-2) Mediated by Disulfide Bond-Induced Dimerization Reveals a Receptor Tyrosine Kinase Dimer Interface. Molecular And Cellular Biology 1998, 18: 5371-5379. PMID: 9710621, PMCID: PMC109122, DOI: 10.1128/mcb.18.9.5371.Peer-Reviewed Original Research3T3 CellsAmino Acid SequenceAmino Acid SubstitutionAnimalsCell LineCell Transformation, NeoplasticCOS CellsCysteineDimerizationDisulfidesDNA PrimersMiceModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedPolymerase Chain ReactionProtein Structure, SecondaryRatsReceptor Protein-Tyrosine KinasesReceptor, ErbB-2Recombinant ProteinsSequence AlignmentSpecificity within the EGF family/ErbB receptor family signaling network
Riese D, Stern D. Specificity within the EGF family/ErbB receptor family signaling network. BioEssays 1998, 20: 41-48. PMID: 9504046, DOI: 10.1002/(sici)1521-1878(199801)20:1<41::aid-bies7>3.0.co;2-v.Peer-Reviewed Original ResearchConceptsErbB family receptorsFamily receptorsEpidermal growth factor (EGF) familyErbB receptor familyGrowth factor familyPeptide growth factorsReceptor couplingHormone-receptor interactionBiological responsesGrowth factorHormoneMultiple receptorsReceptorsReceptor familyCell proliferationErbB familyMultiple hormonesReceptor partnersTyrosine kinaseDiverse biological responsesActivation 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 phosphoproteinsPrognosisAntiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor.
Bangalore L, Tanner AJ, Laudano AP, Stern DF. Antiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor. Proceedings Of The National Academy Of Sciences Of The United States Of America 1992, 89: 11637-11641. PMID: 1280833, PMCID: PMC50608, DOI: 10.1073/pnas.89.23.11637.Peer-Reviewed Original ResearchEGF‐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 factorP185ProteinP185neuReceptorsCellsp185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity.
Stern DF, Heffernan PA, Weinberg RA. p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity. Molecular And Cellular Biology 1986, 6: 1729-1740. PMID: 2878363, PMCID: PMC367701, DOI: 10.1128/mcb.6.5.1729.Peer-Reviewed Original ResearchConceptsTyrosine kinase activityEGF receptorGrowth factor receptorProto-oncogeneKinase activityNeu proto-oncogeneC-erbB geneFactor receptorPresence of tunicamycinDistinct electrophoretic mobilitiesEpidermal growth factor receptorNormal culture conditionsMajor structural alterationsTyrosine phosphorylationGene productsNeu oncogeneNormal homologsOncogeneCell linesElectrophoretic mobilityCulture conditionsGrowth factorP185ProteinReceptors
2020
Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition
Gale M, Li Y, Cao J, Liu ZZ, Holmbeck MA, Zhang M, Lang SM, Wu L, Do Carmo M, Gupta S, Aoshima K, DiGiovanna MP, Stern DF, Rimm DL, Shadel GS, Chen X, Yan Q. Acquired Resistance to HER2-Targeted Therapies Creates Vulnerability to ATP Synthase Inhibition. Cancer Research 2020, 80: 524-535. PMID: 31690671, PMCID: PMC7002225, DOI: 10.1158/0008-5472.can-18-3985.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBreast NeoplasmsCell ProliferationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHumansMiceMice, Inbred NODMice, SCIDMitochondrial Proton-Translocating ATPasesOligomycinsReceptor, ErbB-2TrastuzumabTumor Cells, CulturedXenograft Model Antitumor AssaysConceptsResistant cellsHER2-Targeted TherapyTrastuzumab-resistant tumorsNew therapeutic strategiesNovel potential targetDrug-free mediumAntibody therapySynthase inhibitionLow doseTherapeutic strategiesTrastuzumabBreast tumorsHER2TherapyAcquired ResistanceTumorsPotential targetMitochondrial respirationCellsSelective dependencyInhibitionMinimal changesNovel vulnerabilitiesATP synthase inhibitionOligomycin A
2018
Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in treatment‐resistant melanoma, colorectal, and lung cancer
Theodosakis N, Langdon CG, Micevic G, Krykbaeva I, Means RE, Stern DF, Bosenberg MW. Inhibition of isoprenylation synergizes with MAPK blockade to prevent growth in treatment‐resistant melanoma, colorectal, and lung cancer. Pigment Cell & Melanoma Research 2018, 32: 292-302. PMID: 30281931, PMCID: PMC6590911, DOI: 10.1111/pcmr.12742.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell ProliferationColorectal NeoplasmsDrug Resistance, NeoplasmDrug SynergismHumansHydroxymethylglutaryl-CoA Reductase InhibitorsLung NeoplasmsMaleMelanomaMevalonic AcidMice, NudeMitogen-Activated Protein KinasesPrenylationProtein Kinase InhibitorsProtein Processing, Post-TranslationalSignal TransductionConceptsUseful adjunctive therapyHMG-CoA reductase inhibitorsAnti-tumor effectsAdjunctive therapyInhibition of isoprenylationLung cancerMEK inhibitionReductase inhibitorsMAPK blockadeDriver mutationsAdditional studiesStatinsTherapyMelanomaTumorsVemurafenibMAPK pathwayDownstream metabolitesInhibitionMAPKAdjunctiveColorectalSelumetinibBlockadeCancer
2017
Combinatorial Screening of Pancreatic Adenocarcinoma Reveals Sensitivity to Drug Combinations Including Bromodomain Inhibitor Plus Neddylation Inhibitor
Langdon CG, Platt JT, Means RE, Iyidogan P, Mamillapalli R, Klein M, Held MA, Lee JW, Koo JS, Hatzis C, Hochster HS, Stern DF. Combinatorial Screening of Pancreatic Adenocarcinoma Reveals Sensitivity to Drug Combinations Including Bromodomain Inhibitor Plus Neddylation Inhibitor. Molecular Cancer Therapeutics 2017, 16: 1041-1053. PMID: 28292938, PMCID: PMC5457712, DOI: 10.1158/1535-7163.mct-16-0794.Peer-Reviewed Original ResearchAdenosine TriphosphateAnimalsAntineoplastic AgentsApoptosisCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationDNA DamageDose-Response Relationship, DrugDrug CombinationsDrug Screening Assays, AntitumorDrug SynergismHigh-Throughput Nucleotide SequencingHumansMiceMitochondriaMolecular Targeted TherapyNeoplastic Stem CellsPancreatic NeoplasmsSuperoxidesXenograft Model Antitumor Assays
2016
PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer
Jeong J, VanHouten JN, Dann P, Kim W, Sullivan C, Yu H, Liotta L, Espina V, Stern DF, Friedman PA, Wysolmerski JJ. PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e282-e290. PMID: 26729871, PMCID: PMC4725473, DOI: 10.1073/pnas.1516138113.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCalciumCarcinogenesisCell Line, TumorCell MembraneCell ProliferationCell SurvivalEndocytosisFemaleFluorescent Antibody TechniqueForkhead Box Protein O1Forkhead Transcription FactorsGene Knockdown TechniquesHSP90 Heat-Shock ProteinsHumansImmunoblottingIntracellular SpaceMammary Neoplasms, AnimalMicePlasma Membrane Calcium-Transporting ATPasesProtein BindingProtein TransportReceptor, ErbB-2Signal TransductionSurvival AnalysisConceptsBreast cancerHigh tumor levelsDegradation of HER2Increases Intracellular CalciumMouse mammary tumor virusBreast cancer cellsMammary tumor virusPMCA2 levelsNeu miceTumor levelsFormation of tumorsHER2 levelsIntracellular calciumTherapeutic targetBreast tumorsHER2Milk calciumExpression correlatesCancerHSP 90Mammary glandCancer cellsTumor virusTumorsCalcium
2015
SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells
Langdon CG, Wiedemann N, Held MA, Mamillapalli R, Iyidogan P, Theodosakis N, Platt JT, Levy F, Vuagniaux G, Wang S, Bosenberg MW, Stern DF. SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells. Oncotarget 2015, 6: 37410-37425. PMID: 26485762, PMCID: PMC4741938, DOI: 10.18632/oncotarget.6138.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisApoptosis Regulatory ProteinsAzepinesAzocinesBenzhydryl CompoundsCamptothecinCell Line, TumorCell ProliferationDocetaxelDose-Response Relationship, DrugDrug SynergismFemaleHumansIrinotecanLung NeoplasmsMice, Inbred BALB CMice, NudeNF-kappa BPaclitaxelSignal TransductionTaxoidsTime FactorsTopoisomerase InhibitorsTriazolesTumor BurdenXenograft Model Antitumor AssaysConceptsLung adenocarcinoma cellsDebio 1143Adenocarcinoma cellsOngoing clinical trialsNon-canonical NF-κB signalingTopoisomerase inhibitorsLung adenocarcinoma xenograftsNF-κB signalingBromodomain inhibitor JQ1Clinical trialsConventional chemotherapyTumor volumeVivo treatmentAdenocarcinoma xenograftsAnti-apoptotic proteinsSingle agentCaspase-8 expressionVivo growthInhibitor JQ1Tumor cellsPro-apoptotic protein SmacJQ1Cell linesInhibitorsTaxanesThe broad‐spectrum receptor tyrosine kinase inhibitor dovitinib suppresses growth of BRAF‐mutant melanoma cells in combination with other signaling pathway inhibitors
Langdon CG, Held MA, Platt JT, Meeth K, Iyidogan P, Mamillapalli R, Koo AB, Klein M, Liu Z, Bosenberg MW, Stern DF. The broad‐spectrum receptor tyrosine kinase inhibitor dovitinib suppresses growth of BRAF‐mutant melanoma cells in combination with other signaling pathway inhibitors. Pigment Cell & Melanoma Research 2015, 28: 417-430. PMID: 25854919, PMCID: PMC5215495, DOI: 10.1111/pcmr.12376.Peer-Reviewed Original ResearchConceptsBRAF-mutant melanomaBRAF inhibitorsCell linesCombination of dovitinibBRAF inhibitor treatmentBRAF mutant melanoma cellsBRAF inhibitor resistanceColorectal carcinoma cell linesBRAF-mutant melanoma cell linesMelanoma cell linesCarcinoma cell linesMetastatic melanomaEffective therapyWild-type BRAF cellsInhibitor treatmentAgent inhibitsPathway inhibitorDovitinibInhibitor resistanceMelanoma cellsMelanomaSecond agentInhibitorsTreatmentPDK1 and SGK3 Contribute to the Growth of BRAF-Mutant Melanomas and Are Potential Therapeutic Targets
Scortegagna M, Lau E, Zhang T, Feng Y, Sereduk C, Yin H, De SK, Meeth K, Platt JT, Langdon CG, Halaban R, Pellecchia M, Davies MA, Brown K, Stern DF, Bosenberg M, Ronai ZA. PDK1 and SGK3 Contribute to the Growth of BRAF-Mutant Melanomas and Are Potential Therapeutic Targets. Cancer Research 2015, 75: 1399-1412. PMID: 25712345, PMCID: PMC4383687, DOI: 10.1158/0008-5472.can-14-2785.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzoatesBridged Bicyclo Compounds, HeterocyclicCell Line, TumorDrug Screening Assays, AntitumorG1 Phase Cell Cycle CheckpointsHumansImmediate-Early ProteinsIndazolesLymphatic MetastasisMelanomaMice, KnockoutMolecular Targeted TherapyProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene Proteins B-rafPyrimidinesPyruvate Dehydrogenase Acetyl-Transferring KinaseSkinSkin NeoplasmsConceptsPDK1 inhibitionAGC kinase familySynthetic lethal screenCell cycle arrestPhase cell cycle arrestPigmentation genesPDK1 activityG1 phase cell cycle arrestSuppress melanoma growthKinase familyTherapeutic targetMelanoma growthPDK1PTEN genotypePI3KMelanoma developmentPotential therapeutic targetK inhibitionPharmacologic inhibitionDevelopment of melanomaPan-PI3K inhibitionBRAF-mutant melanomaSGK3GenesMelanoma cells
2014
Overexpression of ERBB4 JM-a CYT-1 and CYT-2 isoforms in transgenic mice reveals isoform-specific roles in mammary gland development and carcinogenesis
Wali VB, Gilmore-Hebert M, Mamillapalli R, Haskins JW, Kurppa KJ, Elenius K, Booth CJ, Stern DF. Overexpression of ERBB4 JM-a CYT-1 and CYT-2 isoforms in transgenic mice reveals isoform-specific roles in mammary gland development and carcinogenesis. Breast Cancer Research 2014, 16: 501. PMID: 25516216, PMCID: PMC4303208, DOI: 10.1186/s13058-014-0501-z.Peer-Reviewed Original ResearchConceptsTerminal end budsBreast cancerRole of ErbB4Transgenic miceCYT-2 isoformsMammary glandKi-67-positive cellsNeoplastic mammary lesionsIsoform-specific rolesBetter therapeutic strategiesMammary gland morphologyEpidermal growth factor receptorMammary terminal end budsMammary ductal morphogenesisErbB4 CYT-2Mammary gland developmentTumor suppressor roleGrowth factor receptorPotential oncogenic functionEarly pregnancyCarcinogenic changesNovel oncogenic propertiesMammary lesionsWhole mount analysisErbB4 expressionSignificance of glioma-associated oncogene homolog 1 (GLI1)expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway
Colavito SA, Zou MR, Yan Q, Nguyen DX, Stern DF. Significance of glioma-associated oncogene homolog 1 (GLI1)expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway. Breast Cancer Research 2014, 16: 444. PMID: 25252859, PMCID: PMC4303124, DOI: 10.1186/s13058-014-0444-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBreast NeoplasmsCell Line, TumorCell MovementCell ProliferationClaudinsEpithelial-Mesenchymal TransitionFemaleGene ExpressionHeterocyclic Compounds, 2-RingHumansMice, Inbred NODMice, SCIDNeoplasm TransplantationNeoplastic Stem CellsNF-kappa BPromoter Regions, GeneticProtein BindingReceptor Cross-TalkRNA, MessengerSignal TransductionThiazolesTranscription FactorsZinc Finger Protein GLI1ConceptsGlioma-associated oncogene homolog 1Claudin-low cell linesBreast cancer stem cellsCancer stem cellsOncogene homolog 1Gli1 expressionBreast cancerClaudin-low breast cancer subtypeMetastatic breast cancer stem cellsNFκB pathwayCell linesClaudin-low breast cancerActivated B cells (NF-κB) pathwayClaudin-low subtypeHomolog 1Breast cancer subtypesMarkers of EMTB-cell pathwayNFκB subunit p65Stem cellsMesenchymal-like characteristicsPoor prognosisTreatment optionsOrthotopic xenograftsAggressive type
2013
EGF 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 investigation
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