2016
GNA14 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
2013
Clonal growth of human melanocytes using cell‐free extracellular matrix
Zhang R, Premi S, Kilic SS, Bacchiocchi A, Halaban R, Brash DE. Clonal growth of human melanocytes using cell‐free extracellular matrix. Pigment Cell & Melanoma Research 2013, 26: 925-927. PMID: 24034857, PMCID: PMC4086752, DOI: 10.1111/pcmr.12159.Peer-Reviewed Original Research
2011
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 migrationHER3KnockdownIGF1R
2008
MEDME: An experimental and analytical methodology for the estimation of DNA methylation levels based on microarray derived MeDIP-enrichment
Pelizzola M, Koga Y, Urban AE, Krauthammer M, Weissman S, Halaban R, Molinaro AM. MEDME: An experimental and analytical methodology for the estimation of DNA methylation levels based on microarray derived MeDIP-enrichment. Genome Research 2008, 18: 1652-1659. PMID: 18765822, PMCID: PMC2556264, DOI: 10.1101/gr.080721.108.Peer-Reviewed Original ResearchConceptsDNA methylation levelsDNA methylationMethylation levelsRelative DNA methylation levelsChromosome-wide levelBisulfite genomic DNA sequencingGenome-wide studiesMelanoma cell strainsDNA methylation statusGenomic DNA sequencingTranscriptional machineryNormal human melanocytesMethylated CpGsMethylated fragmentsEpigenetic modificationsMethylation estimatesHigh-throughput settingHuman diseasesHuman melanocytesMethylationMethylation statusDNA sequencingAntibody enrichmentGenomeCell strains
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
2005
Melanocyte and Keratinocyte Carcinogenesis: p53 Family Protein Activities and Intersecting mRNA Expression Profiles
Kulesz-Martin M, Lagowski J, Fei S, Pelz C, Sears R, Powell MB, Halaban R, Johnson J. Melanocyte and Keratinocyte Carcinogenesis: p53 Family Protein Activities and Intersecting mRNA Expression Profiles. Journal Of Investigative Dermatology Symposium Proceedings 2005, 10: 142-152. PMID: 16363065, DOI: 10.1111/j.1087-0024.2005.200405.x.Peer-Reviewed Original ResearchRb/E2F: A two-edged sword in the melanocytic system
Halaban R. Rb/E2F: A two-edged sword in the melanocytic system. Cancer And Metastasis Reviews 2005, 24: 339-356. PMID: 15986142, DOI: 10.1007/s10555-005-1582-z.Peer-Reviewed Original ResearchConceptsE2F transcriptional activityTranscriptional activityActivated cell surface receptorsRb/E2F pathwayRb-E2F interactionCyclin-dependent kinase activityCell cycle genesE2F complex formationMelanoma cellsCdk inhibitors p16INK4ACell cycle progressionDependent kinase activityExpression of E2FCell surface receptorsGene repressionCycle genesE2F pathwayCDK activityApoptosis genesKinase activityB-RafCycle progressionRb interactionPhosphorylated RbTumor suppressor
2004
Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas
Hoek K, Rimm DL, Williams KR, Zhao H, Ariyan S, Lin A, Kluger HM, Berger AJ, Cheng E, Trombetta ES, Wu T, Niinobe M, Yoshikawa K, Hannigan GE, Halaban R. Expression Profiling Reveals Novel Pathways in the Transformation of Melanocytes to Melanomas. Cancer Research 2004, 64: 5270-5282. PMID: 15289333, DOI: 10.1158/0008-5472.can-04-0731.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkers, TumorCell Transformation, NeoplasticCohort StudiesDown-RegulationGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLymphatic MetastasisMelanocytesMelanomaMiceNuclear ProteinsOligonucleotide Array Sequence AnalysisPrognosisSignal TransductionSkin NeoplasmsSurvival RateTranscription FactorsTransfectionTwist-Related Protein 1Ubiquitin ThiolesteraseConceptsGlobal differential gene expressionMembrane trafficking eventsNovel pathwayNormal melanocytesHelix protein TwistAdditional transcriptional regulatorsDifferential gene expressionMelanoma cellsTransformation of melanocytesCpG promoter methylationNormal human melanocytesTrafficking eventsTranscriptional regulatorsEmbryonic developmentGrowth suppressorChromosomal regionsExpression profilingGene expressionNotch pathwayOligonucleotide microarraysMelanoma tissue microarrayDifferential expressionGenesHuman melanocytesGrowth advantageCarbohydrates 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 interactionsMaturationMelanocytesTyrosinaseCellsCalnexinMisfoldingERThe tyrphostin AG1024 accelerates the degradation of phosphorylated forms of retinoblastoma protein (pRb) and restores pRb tumor suppressive function in melanoma cells.
von Willebrand M, Zacksenhaus E, Cheng E, Glazer P, Halaban R. The tyrphostin AG1024 accelerates the degradation of phosphorylated forms of retinoblastoma protein (pRb) and restores pRb tumor suppressive function in melanoma cells. Cancer Research 2003, 63: 1420-9. PMID: 12649208.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCell DivisionCyclin-Dependent KinasesDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorE2F3 Transcription FactorHumansMAP Kinase Signaling SystemMelanocytesMelanomaMiceMitogen-Activated Protein Kinase 1PhosphorylationRetinoblastoma ProteinTranscription FactorsTyrphostinsUbiquitinConceptsTumor suppressive functionPhosphorylated formCell surface receptor kinaseMitogen-activated protein kinase/extracellular signal-regulated kinase pathwayProtein kinase/extracellular signal-regulated kinase pathwayExtracellular signal-regulated kinase (ERK) pathwaySignal-regulated kinase pathwayMelanoma cellsPhosphorylation/inactivationCyclin-dependent kinase 2Insulin-like growth factor 1 receptorActivation of pRbReceptor kinase activitySpecific chemical inhibitorsGrowth factor 1 receptorFactor 1 receptorPocket proteinsRetinoblastoma familyMelanoma cell proliferationReceptor kinaseProtein degradationKinase pathwayRetinoblastoma proteinKinase activityMelanoma cell growth
2000
Translation 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
1999
Melanoma Cell Autonomous Growth: The Rb/E2F Pathway
Halaban R. Melanoma Cell Autonomous Growth: The Rb/E2F Pathway. Cancer And Metastasis Reviews 1999, 18: 333-343. PMID: 10721488, DOI: 10.1023/a:1006396104073.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell CycleCell Cycle ProteinsCell DivisionCyclin-Dependent KinasesDNA-Binding ProteinsE2F Transcription FactorsHumansMelanocytesMelanomaPhosphorylationRetinoblastoma ProteinRetinoblastoma-Binding Protein 1Signal TransductionTranscription Factor DP1Transcription FactorsConceptsPocket proteinsExternal growth factorsNormal melanocytesE2F activityTarget genesRb/E2F pathwayE2F transcription factorsCell surface receptor stimulationMelanoma cellsCell-autonomous growthTumor suppressor proteinClass of enzymesCyclin-dependent kinasesInactivation of pRbConstitutive high expressionGrowth factorCell cycle progressionSurface receptor stimulationMetastatic melanoma cellsRetinoblastoma familySuppressive complexE2F pathwayPositive regulatorTranscription factorsMouse melanocytes
1998
Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1
Halaban R, Cheng E, Zhang Y, Mandigo C, Miglarese M. Release of cell cycle constraints in mouse melanocytes by overexpressed mutant E2F1E132, but not by deletion of p16INK4A or p21WAF1/CIP1. Oncogene 1998, 16: 2489-2501. PMID: 9627115, DOI: 10.1038/sj.onc.1201773.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell CycleCell Cycle ProteinsCell SurvivalCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21CyclinsDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorGene Expression RegulationHumansMelanocytesMiceMice, NudeMutagenesisProtein BiosynthesisRecombinant Fusion ProteinsRetinoblastoma ProteinRetinoblastoma-Binding Protein 1Tetradecanoylphorbol AcetateTranscription Factor DP1Transcription FactorsConceptsP21WAF1/CIP1Cell cycle progressionMouse melanocytesTarget genesCycle progressionRetinoblastoma tumor suppressor proteinE2F-mediated transactivationCell cycle constraintsTumor suppressor proteinRole of E2F1Deletion of p16INK4AFree E2FExpression of RbGene disruptionSuppressor proteinEctopic expressionHallmark of melanomaTetradecanoyl phorbol 13Loss of p16INK4aConstitutive expressionMelanoma cell linesCell deathNormal melanocytesIndependent growthMelanocyte growth
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 forms
1996
Growth factors and melanomas.
Halaban R. Growth factors and melanomas. Seminars In Oncology 1996, 23: 673-81. PMID: 8970586.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCell Cycle ProteinsCell Transformation, NeoplasticCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent KinasesEndothelinsFibroblast Growth Factor 2Gene Expression Regulation, NeoplasticGrowth SubstancesHumansMelanocytesMelanomaReceptors, Growth FactorSignal TransductionConceptsCyclin-dependent kinasesFibroblast growth factorNormal human melanocytesMast/stem cell growth factorCell cycleCDK inhibitor p16INK4Human melanocytesMelanoma cellsGrowth factorHepatocyte growth factor/scatter factorStem cell growth factorGrowth factor/scatter factorSynergistic growth factorsNeuropeptide endothelin-1Cell cycle progressionPhosphorylation of retinoblastomaGrowth constraintsWild-type p53Unregulated expressionTranscriptional activityNegative regulatorCycle progressionResult of inactivationBasic fibroblast growth factorInhibitory complex