2016
A generic, cost-effective, and scalable cell lineage analysis platform
Biezuner T, Spiro A, Raz O, Amir S, Milo L, Adar R, Chapal-Ilani N, Berman V, Fried Y, Ainbinder E, Cohen G, Barr H, Halaban R, Shapiro E. A generic, cost-effective, and scalable cell lineage analysis platform. Genome Research 2016, 26: 1588-1599. PMID: 27558250, PMCID: PMC5088600, DOI: 10.1101/gr.202903.115.Peer-Reviewed Original ResearchConceptsLineage analysisSingle cell lineage analysisSingle-cell sequencing dataSingle-cell genomicsCurrent sequencing-based methodsIndividual cellsCell lineage analysisSingle-cell sequencingSequencing-based methodsLineage treesSequencing dataLineage relationsCellsTreesGenomicsAnalysis platformInput cellsSequencingBulk analysisVivoDiscoveryLandscapeGNA14 Somatic Mutation Causes Congenital and Sporadic Vascular Tumors by MAPK Activation
Lim YH, Bacchiocchi A, Qiu J, Straub R, Bruckner A, Bercovitch L, Narayan D, Genomics Y, McNiff J, Ko C, Robinson-Bostom L, Antaya R, Halaban R, Choate KA. GNA14 Somatic Mutation Causes Congenital and Sporadic Vascular Tumors by MAPK Activation. American Journal Of Human Genetics 2016, 99: 443-450. PMID: 27476652, PMCID: PMC4974082, DOI: 10.1016/j.ajhg.2016.06.010.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedChild, PreschoolEnzyme ActivationGTP-Binding Protein alpha SubunitsGTP-Binding Protein alpha Subunits, Gq-G11Human Umbilical Vein Endothelial CellsHumansInfantInfant, NewbornIntercellular Signaling Peptides and ProteinsMaleMAP Kinase Signaling SystemMelanocytesMitogen-Activated Protein KinasesMutationProto-Oncogene Proteins c-aktVascular NeoplasmsConceptsLobular capillary hemangiomaVascular tumorsKaposiform hemangioendotheliomaMonths of lifeYears of ageSomatic activating mutationsGNA14 mutationsHuman endothelial cellsPharmacologic interventionsSignificant complicationsCommon neoplasmCapillary hemangiomaInfantile hemangiomasLCH lesionsPrimary human endothelial cellsTherapeutic interventionsActivating mutationsGNA11 mutationsTumorsEndothelial cellsLesionsPotential targetHemangiomaGNA14Somatic mutations
2015
Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure
Premi S, Wallisch S, Mano CM, Weiner AB, Bacchiocchi A, Wakamatsu K, Bechara EJ, Halaban R, Douki T, Brash DE. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Science 2015, 347: 842-847. PMID: 25700512, PMCID: PMC4432913, DOI: 10.1126/science.1256022.Peer-Reviewed Original ResearchConceptsDark cyclobutane pyrimidine dimersExcited electronic statesUltraviolet photonsUV photonsElectronic statesTriplet stateSunlight-induced melanomaCytosine-containing cyclobutane pyrimidine dimersEnergy transferPhotonsPicosecondsElectronsUV exposureRadiationChemiexcitationEnergyStatePhotoproducts
2009
Genome-wide screen of promoter methylation identifies novel markers in melanoma
Koga Y, Pelizzola M, Cheng E, Krauthammer M, Sznol M, Ariyan S, Narayan D, Molinaro AM, Halaban R, Weissman SM. Genome-wide screen of promoter methylation identifies novel markers in melanoma. Genome Research 2009, 19: 1462-1470. PMID: 19491193, PMCID: PMC2720187, DOI: 10.1101/gr.091447.109.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAgedBiomarkers, TumorCells, CulturedCluster AnalysisCollagenCollagen Type IDNA MethylationFemaleGene Expression ProfilingGenome, HumanGenome-Wide Association StudyHSP20 Heat-Shock ProteinsHumansInfant, NewbornMaleMelanomaMetallothioneinMiddle AgedMolecular ChaperonesNuclear ProteinsNucleoplasminsOligonucleotide Array Sequence AnalysisPhosphoproteinsPromoter Regions, GeneticProteinsReproducibility of ResultsReverse Transcriptase Polymerase Chain ReactionSequence Analysis, DNATumor Cells, CulturedConceptsDifferential gene expressionGene expressionPromoter methylationGenome-wide promoter methylationGenome-wide integrative analysisPromoter CpG contentMethylation markersGenome-wide screenSequencing of bisulfiteTranscription start siteMelanoma cell strainsCell strainsTranscriptional machineryNovel genesEpigenetic modificationsDNA methylationIdentifies novel markersStart siteSnap-frozen tissuesCpG contentAdult melanocytesIntegrative analysisReal-time reverse transcriptase PCRHuman diseasesMethylation
2007
XAF1 Mediates Tumor Necrosis Factor-α-induced Apoptosis and X-linked Inhibitor of Apoptosis Cleavage by Acting through the Mitochondrial Pathway*
Straszewski-Chavez SL, Visintin IP, Karassina N, Los G, Liston P, Halaban R, Fadiel A, Mor G. XAF1 Mediates Tumor Necrosis Factor-α-induced Apoptosis and X-linked Inhibitor of Apoptosis Cleavage by Acting through the Mitochondrial Pathway*. Journal Of Biological Chemistry 2007, 282: 13059-13072. PMID: 17329253, DOI: 10.1074/jbc.m609038200.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingApoptosisApoptosis Regulatory ProteinsCell SurvivalCells, CulturedFas ReceptorFemaleHumansIntracellular Signaling Peptides and ProteinsMitochondriaNeoplasm ProteinsPregnancyPregnancy Trimester, FirstPregnancy Trimester, ThirdTrophoblastsTumor Necrosis Factor-alphaX-Linked Inhibitor of Apoptosis ProteinConceptsThird trimester trophoblast cellsOverexpression of XAF1Fas ligand-induced apoptosisCaspase inhibitory activityTNF-alpha-induced apoptosisMembrane-bound death receptorsNovel regulatory pathwayLigand-induced apoptosisTrophoblast cellsXIAP inactivationMitochondrial pathwayRegulatory pathwaysDeath receptorsProapoptotic proteinsMolecular mechanismsApoptotic cascadeFirst trimester trophoblast cellsDifferential expressionXAF1XAF1 expressionCell survivalInduces ApoptosisGene methylationApoptosisPathway
2006
Rab33A: Characterization, Expression, and Suppression by Epigenetic Modification
Cheng E, Trombetta SE, Kovacs D, Beech RD, Ariyan S, Reyes-Mugica M, McNiff JM, Narayan D, Kluger HM, Picardo M, Halaban R. Rab33A: Characterization, Expression, and Suppression by Epigenetic Modification. Journal Of Investigative Dermatology 2006, 126: 2257-2271. PMID: 16810302, DOI: 10.1038/sj.jid.5700386.Peer-Reviewed Original ResearchConceptsX chromosome-linked geneSpecific gene expressionTranscription initiation siteSpecific promoter regionsMelanoma cellsGTPase mutantsEpigenetic modificationsSmall GTPaseDNA methylationVesicular transportRab33AGene expressionPromoter regionMelanosomal proteinsInitiation siteNormal melanocytesAberrant downregulationGenesEarly eventsAberrant processesMelanocytesExpressionGTPaseImportant roleNormal process
2004
Carbohydrates act as sorting determinants in ER-associated degradation of tyrosinase
Svedine S, Wang T, Halaban R, Hebert DN. Carbohydrates act as sorting determinants in ER-associated degradation of tyrosinase. Journal Of Cell Science 2004, 117: 2937-2949. PMID: 15161941, DOI: 10.1242/jcs.01154.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCalnexinCarbohydrate MetabolismCells, CulturedEndoplasmic ReticulumEndoplasmic Reticulum Chaperone BiPGlucoseHeat-Shock ProteinsMannoseMelanocytesMiceMolecular ChaperonesMonophenol MonooxygenaseMutationProteasome Endopeptidase ComplexProtein Disulfide-IsomerasesProtein TransportConceptsLectin chaperonesMutant tyrosinaseEndoplasmic reticulum (ER) quality control machineryQuality control machineryProtein disulfide isomeraseDegradation of tyrosinaseERAD substratesChaperone interactionsNon-native substratesER organizationProtein maturationER retentionER lumenDisulfide isomeraseAberrant proteinsProteasomal degradationGlucose trimmingProtein degradationProtein aggregatesTyrosinase degradationSubsequent degradationChaperonesIntact melanocytesMaturation processProteasome
2003
Tyrosinase Maturation and Oligomerization in the Endoplasmic Reticulum Require a Melanocyte-specific Factor*
Francis E, Wang N, Parag H, Halaban R, Hebert DN. Tyrosinase Maturation and Oligomerization in the Endoplasmic Reticulum Require a Melanocyte-specific Factor*. Journal Of Biological Chemistry 2003, 278: 25607-25617. PMID: 12724309, DOI: 10.1074/jbc.m303411200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalnexinCalreticulinCells, CulturedCentrifugation, Density GradientCHO CellsCricetinaeCross-Linking ReagentsDimerizationDogsElectrophoresis, Polyacrylamide GelEndoplasmic ReticulumLectinsMelanocytesMembrane GlycoproteinsMiceMicrosomesMonophenol MonooxygenaseMutationOxidoreductasesPancreasPlasmidsPolysaccharidesProtein BindingProtein BiosynthesisProtein FoldingProtein TransportProteinsRabbitsSucroseTime FactorsTranscription, GeneticTrypsinConceptsMelanocyte-specific factorsSemipermeabilized cellsEndoplasmic reticulum retentionLectin chaperones calnexinMelanocyte-specific proteinsTyrosinase-related protein 1Wild-type tyrosinaseSynthesis of melaninChaperone interactionsChaperone calnexinTyrosinase maturationMouse melanocytesTrypsin-resistant stateProtein 1Human tyrosinaseTranslation systemOligomerizationPersistent interactionsMaturationMelanocytesTyrosinaseCellsCalnexinMisfoldingER
2002
Coexpression of Wild-Type Tyrosinase Enhances Maturation of Temperature-Sensitive Tyrosinase Mutants
Halaban R, Cheng E, Hebert DN. Coexpression of Wild-Type Tyrosinase Enhances Maturation of Temperature-Sensitive Tyrosinase Mutants. Journal Of Investigative Dermatology 2002, 119: 481-488. PMID: 12190874, DOI: 10.1046/j.1523-1747.2002.01824.x.Peer-Reviewed Original ResearchConceptsWild-type proteinTyrosinase mutantsMutant proteinsGlycosylation-deficient mutantsGlycosylation-deficient formsOculocutaneous albinism 1Wild-type tyrosinaseDevelopment of pigmentsDifferent mutant allelesType I membraneActivity-dependent mannerNonpermissive temperatureMutant allelesEndoplasmic reticulumTypes of mutationsMutantsFunction mutationsCarbohydrate processingMelanin synthesisProteinCoexpressionMelanocytesTyrosinase activityMutationsMaturationAbnormal Acidification of Melanoma Cells Induces Tyrosinase Retention in the Early Secretory Pathway*
Halaban R, Patton RS, Cheng E, Svedine S, Trombetta ES, Wahl ML, Ariyan S, Hebert DN. Abnormal Acidification of Melanoma Cells Induces Tyrosinase Retention in the Early Secretory Pathway*. Journal Of Biological Chemistry 2002, 277: 14821-14828. PMID: 11812790, DOI: 10.1074/jbc.m111497200.Peer-Reviewed Original Research
2000
Proper Folding and Endoplasmic Reticulum to Golgi Transport of Tyrosinase Are Induced by Its Substrates, DOPA and Tyrosine*
Halaban R, Cheng E, Svedine S, Aron R, Hebert D. Proper Folding and Endoplasmic Reticulum to Golgi Transport of Tyrosinase Are Induced by Its Substrates, DOPA and Tyrosine*. Journal Of Biological Chemistry 2000, 276: 11933-11938. PMID: 11124258, DOI: 10.1074/jbc.m008703200.Peer-Reviewed Original ResearchConceptsWild-type tyrosinaseEndoplasmic reticulumProper foldingWild-type proteinMelanoma cellsLoss of pigmentationTyrosinase-positive melanoma cellsGolgi transportType proteinAlbino mutantS proteasomeSubsequent retranslocationMutant formsCatalytic stateEnzymatic activityProteolytic degradationNative formReticulumFoldingProteinTumor-derived antigenic peptidesTyrosinase activitySuppress tyrosinase activityCellsMetabolic changesTranslation Rate of Human Tyrosinase Determines ItsN-Linked Glycosylation Level*
Újvári A, Aron R, Eisenhaure T, Cheng E, Parag H, Smicun Y, Halaban R, Hebert D. Translation Rate of Human Tyrosinase Determines ItsN-Linked Glycosylation Level*. Journal Of Biological Chemistry 2000, 276: 5924-5931. PMID: 11069924, DOI: 10.1074/jbc.m009203200.Peer-Reviewed Original ResearchConceptsTranslation rateCell-free systemProtein translation ratesType I membrane glycoproteinsNormal melanocytesHuman tyrosinaseSemi-permeabilized cellsMelanoma cellsUbiquitin-proteasomal pathwayRate of translationSite-directed mutagenesisWild-type tyrosinaseProtein synthesis inhibitor cycloheximideInefficient glycosylationGlycosylation efficiencyAberrant retentionProtein translationCotranslational eventsConsensus sitesCore glycanDegradative fateProtein doubletEndoplasmic reticulumMaturation eventsAmelanotic melanoma cellsEndoplasmic reticulum retention is a common defect associated with tyrosinase-negative albinism
Halaban R, Svedine S, Cheng E, Smicun Y, Aron R, Hebert D. Endoplasmic reticulum retention is a common defect associated with tyrosinase-negative albinism. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 5889-5894. PMID: 10823941, PMCID: PMC18529, DOI: 10.1073/pnas.97.11.5889.Peer-Reviewed Original ResearchMeSH KeywordsAlbinism, OculocutaneousAmino Acid SubstitutionAnimalsCalcium-Binding ProteinsCalnexinCalreticulinCells, CulturedEndoplasmic ReticulumGolgi ApparatusHumansMelanocytesMelanosomesMiceMice, Mutant StrainsMicroscopy, FluorescenceMonophenol MonooxygenasePoint MutationProtein BindingProtein FoldingRecombinant Fusion ProteinsRibonucleoproteinsTransfectionDeregulated E2f Transcriptional Activity in Autonomously Growing Melanoma Cells
Halaban R, Cheng E, Smicun Y, Germino J. Deregulated E2f Transcriptional Activity in Autonomously Growing Melanoma Cells. Journal Of Experimental Medicine 2000, 191: 1005-1016. PMID: 10727462, PMCID: PMC2193116, DOI: 10.1084/jem.191.6.1005.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCell Cycle ProteinsCell DivisionCells, CulturedCellular SenescenceCulture Media, ConditionedCyclin-Dependent KinasesCyclinsDNA-Binding ProteinsDown-RegulationDrosophila ProteinsE2F Transcription FactorsE2F1 Transcription FactorE2F2 Transcription FactorE2F3 Transcription FactorE2F4 Transcription FactorE2F5 Transcription FactorE2F6 Transcription FactorEnzyme InhibitorsFlavonoidsHumansMelanocytesMelanomaPhosphorylationPiperidinesProtein BindingRetinoblastoma-Binding Protein 1Trans-ActivatorsTranscription Factor DP1Transcription FactorsTumor Cells, CulturedConceptsExternal growth factorsE2F DNAPocket proteinsCyclin-dependent kinase 4Normal melanocytesTranscriptional activityRetinoblastoma tumor suppressor proteinMelanoma cellsMalignant human melanocytesE2F transcription factorsE2F family membersE2F transcriptional activityTumor suppressor proteinGel shift analysisCell cycle progressionForm of pRBGrowth factorContinuous high expressionE2F activityOnly family memberTranscription factorsProtein DNASuppressor proteinFamily membersMolecular basisThe Regulation of Normal Melanocyte Proliferation
Halaban R. The Regulation of Normal Melanocyte Proliferation. Pigment Cell & Melanoma Research 2000, 13: 4-14. PMID: 10761990, DOI: 10.1034/j.1600-0749.2000.130103.x.Peer-Reviewed Original ResearchConceptsTranscription factorsIntracellular signal transduction cascadesE2F transcription factorsImmediate early response genesSignal transduction cascadeHepatocyte growth factor/scatter factorGrowth factorGrowth factor/scatter factorE2F transcriptional activityCyclin-dependent kinasesSynergistic growth factorsNormal human melanocytesPocket proteinsRetinoblastoma familyPeptide growth factorsStem cell factorTransduction cascadeNormal melanocyte proliferationEctopic expressionResponse genesTranscriptional activityFibroblast growth factorMolecular eventsHuman melanocytesIntermediate effectors
1997
Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells
Halaban R, Cheng E, Zhang Y, Moellmann G, Hanlon D, Michalak M, Setaluri V, Hebert D. Aberrant retention of tyrosinase in the endoplasmic reticulum mediates accelerated degradation of the enzyme and contributes to the dedifferentiated phenotype of amelanotic melanoma cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 6210-6215. PMID: 9177196, PMCID: PMC21028, DOI: 10.1073/pnas.94.12.6210.Peer-Reviewed Original ResearchMeSH KeywordsAdultCalcium-Binding ProteinsCalnexinCalreticulinCell DifferentiationCells, CulturedCoculture TechniquesEndoplasmic ReticulumEnzyme PrecursorsHumansInfant, NewbornKineticsMelanocytesMelanomaMolecular ChaperonesMolecular WeightMonophenol MonooxygenasePhenotypeRibonucleoproteinsSkin NeoplasmsTime FactorsTumor Cells, CulturedConceptsEndoplasmic reticulumNormal melanocytesER chaperone calnexinMelanin synthesisMalignant melanocytesMelanoma cellsChaperone bindingAberrant retentionChaperone calnexinGolgi compartmentSubcellular localizationAmelanotic melanoma cell lineKey enzymeMelanoma cell linesMaturation of tyrosinaseAmelanotic melanoma cellsKinetics of synthesisInhibitor sensitivityDedifferentiated phenotypeProteolytic degradationCell linesProteasome inhibitorsEnzymeProteasomeImmature formsRecognition of activated CSF-1 receptor in breast carcinomas by a tyrosine 723 phosphospecific antibody
Flick M, Sapi E, Perrotta P, Maher M, Halaban R, Carter D, Kacinski B. Recognition of activated CSF-1 receptor in breast carcinomas by a tyrosine 723 phosphospecific antibody. Oncogene 1997, 14: 2553-2561. PMID: 9191055, DOI: 10.1038/sj.onc.1201092.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodiesAntibody SpecificityBreast NeoplasmsCarcinoma in SituCells, CulturedCross ReactionsEpitopesFibroblastsGenes, fmsHumansImmunohistochemistryMacrophagesMiceMice, Inbred BALB CPhosphopeptidesPhosphorylationPhosphotyrosineProto-Oncogene MasReceptor, Macrophage Colony-Stimulating FactorTumor Cells, CulturedConceptsCSF-1RMultiple signal transduction pathwaysC-fms proto-oncogenePhosphorylation state-specific antibodiesSignal transduction pathwaysCSF-1 receptorAnchorage-independent growthImmunoblots of lysatesActivation/phosphorylationEffector proteinsVivo phosphorylationCytoplasmic domainDifferentiation of macrophagesPhosphospecific antibodiesTransduction pathwaysCellular phenotypesInvasive human breast tumoursSpecific phosphopeptidesC-fms oncogeneCSF-1Proto-oncogeneHuman breast carcinomaFirst direct evidenceNormal proliferationFactor receptor
1995
Identification of p90RSK as the probable CREB-Ser133 kinase in human melanocytes.
Böhm M, Moellmann G, Cheng E, Alvarez-Franco M, Wagner S, Sassone-Corsi P, Halaban R. Identification of p90RSK as the probable CREB-Ser133 kinase in human melanocytes. Molecular Cancer Research 1995, 6: 291-302. PMID: 7540859.Peer-Reviewed Original ResearchMeSH KeywordsCell CountCell DivisionCells, CulturedCyclic AMPCyclic AMP Response Element-Binding ProteinDrug SynergismEndothelinsFibroblast Growth Factor 2Growth SubstancesHematopoietic Cell Growth FactorsHepatocyte Growth FactorHumansInfant, NewbornMelanocytesPhosphorylationProtein Serine-Threonine KinasesRecombinant Fusion ProteinsRibosomal Protein S6 KinasesSerineStem Cell FactorTime FactorsTranscription FactorsConceptsSynergistic growth factorsMast/stem cell growth factorHuman melanocytesGrowth factorHepatocyte growth factor/scatter factorActivation of p90RSKGrowth factor/scatter factorStem cell growth factorCAMP-responsive element binding proteinKID domainElement-binding proteinNormal human melanocytesTranscription factor 1Peptide growth factorsSer133 phosphorylationTranscriptional activationCell divisionPhosphorylated stateTranscription factorsInduces phosphorylationRegulatory proteinsSignal transducerFibroblast growth factorBasic fibroblast growth factorBinding proteinMouse silver. mutation is caused by a single base insertion in the putative cytoplasmic domain of Pmel 17
Kwon B, Halaban R, Ponnazhagan S, Kim K, Chintamaneni C, Bennett D, Pickard R. Mouse silver. mutation is caused by a single base insertion in the putative cytoplasmic domain of Pmel 17. Nucleic Acids Research 1995, 23: 154-158. PMID: 7870580, PMCID: PMC306643, DOI: 10.1093/nar/23.1.154.Peer-Reviewed Original ResearchConceptsPmel 17CDNA clonesMelanocyte cDNA libraryPutative cytoplasmic tailPutative cytoplasmic domainAmino acidsMouse chromosome 10Coat color locusSingle nucleotide insertionSilver locusSingle base insertionChromosomal locationGenomic regionsCytoplasmic domainTermination signalCytoplasmic tailCDNA libraryReading frameSI allelesColor locusCarboxyl terminusC-terminusChromosome 10Nucleotide insertionBase insertion
1993
Altered Metabolism of Mast-Cell Growth Factor (c-kit Ligand) in Cutaneous Mastocytosis
Longley B, Morganroth G, Tyrrell L, Ding T, Anderson D, Williams D, Halaban R. Altered Metabolism of Mast-Cell Growth Factor (c-kit Ligand) in Cutaneous Mastocytosis. New England Journal Of Medicine 1993, 328: 1302-1307. PMID: 7682288, DOI: 10.1056/nejm199305063281803.Peer-Reviewed Original ResearchConceptsMast cell growth factorMessenger RNAGrowth factorC-kit proto-oncogeneProduction of melaninSoluble formGrowth factor geneFactor genesProteolytic processingProto-oncogeneSequence abnormalitiesExtracellular spaceAltered metabolismAltered distributionGrowth factor messenger RNASkin of patientsDermal cellsCellsPolymerase chain reactionCutaneous mastocytosisMast cells