2014
Identification of PLX4032‐resistance mechanisms and implications for novel RAF inhibitors
Choi J, Landrette SF, Wang T, Evans P, Bacchiocchi A, Bjornson R, Cheng E, Stiegler AL, Gathiaka S, Acevedo O, Boggon TJ, Krauthammer M, Halaban R, Xu T. Identification of PLX4032‐resistance mechanisms and implications for novel RAF inhibitors. Pigment Cell & Melanoma Research 2014, 27: 253-262. PMID: 24283590, PMCID: PMC4065135, DOI: 10.1111/pcmr.12197.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell Line, TumorCell ProliferationDNA Transposable ElementsDrug Resistance, NeoplasmHumansIndolesMAP Kinase Signaling SystemMelanomaModels, MolecularMolecular Sequence DataMutagenesis, InsertionalMutant ProteinsMutationProtein Kinase InhibitorsProto-Oncogene Proteins B-rafSulfonamidesVemurafenibConceptsBRAF mutationsNovel BRAF mutationBRAF inhibitorsNext-generation BRAF inhibitorsPLX4032-resistant melanoma cellsMelanoma cellsMelanoma patient survivalHuman prostate cancerBRAF mutant cellsWhole-exome sequencingMelanoma patientsPatient survivalClinical trialsProstate cancerRAF inhibitorsOncogenic mutationsNew screening approachRelevant aberrationsInhibitorsCellsMutationsScreening approachNovel RAF inhibitorsPatientsPLX8394
2012
Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate
Ha BH, Davis MJ, Chen C, Lou HJ, Gao J, Zhang R, Krauthammer M, Halaban R, Schlessinger J, Turk BE, Boggon TJ. Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 16107-16112. PMID: 22988085, PMCID: PMC3479536, DOI: 10.1073/pnas.1214447109.Peer-Reviewed Original ResearchConceptsP21-activated kinasePhosphorylated activation loopActivation loop phosphorylationCritical proline residueRho family GTPasesBcl-2/BclCellular morphological changesPAK regulationStructure-guided approachLoop phosphorylationPseudosubstrate regionAutoinhibitory pseudosubstratePseudosubstrate motifActivation loopCatalytic domainSrc SH3Cell motilityMolecular basisProline residuesKey effectorsCell deathPAK4SH3KinasePseudosubstrate
2010
Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032
Rubinstein JC, Sznol M, Pavlick AC, Ariyan S, Cheng E, Bacchiocchi A, Kluger HM, Narayan D, Halaban R. Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032. Journal Of Translational Medicine 2010, 8: 67. PMID: 20630094, PMCID: PMC2917408, DOI: 10.1186/1479-5876-8-67.Peer-Reviewed Original ResearchConceptsV600K mutationsClinical trialsBRAF V600E/K mutationK mutationPotential therapeutic responseMutant BRAF inhibitorsBRAF inhibitor PLX4032BRAF V600K mutationMelanoma patientsTherapeutic responseBRAF mutationsPatientsV600E mutationInhibitor PLX4032BRAF kinasePLX4032TrialsCommon mutationsMutationsMelanomaIncidence
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
1998
Identification of morc (microrchidia), a mutation that results in arrest of spermatogenesis at an early meiotic stage in the mouse
Watson M, Zinn A, Inoue N, Hess K, Cobb J, Handel M, Halaban R, Duchene C, Albright G, Moreadith R. Identification of morc (microrchidia), a mutation that results in arrest of spermatogenesis at an early meiotic stage in the mouse. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 14361-14366. PMID: 9826705, PMCID: PMC24378, DOI: 10.1073/pnas.95.24.14361.Peer-Reviewed Original ResearchConceptsMammalian germ cell developmentGerm cellsGerm cell developmentNovel biochemical pathwaysEarly meiotic stagesTransgene expressionMale gametogenesisMouse strain transgenicGenomic analysisProphase IMutant animalsTransgene insertionCDNA constructsEye pigmentationBiochemical pathwaysLeptotene stageAbnormal phenotypeCell developmentMeiotic stagesMeiosisMutation resultsArrest of spermatogenesisGenesSpermatogenesisMutations
1996
Growth Regulatory Proteins that Repress Differentiation Markers in Melanocytes Also Downregulate the Transcription Factor Microphthalmia
Halaban R, Böhm M, Dotto P, Moellmann G, Cheng E, Zhang Y. Growth Regulatory Proteins that Repress Differentiation Markers in Melanocytes Also Downregulate the Transcription Factor Microphthalmia. Journal Of Investigative Dermatology 1996, 106: 1266-1272. PMID: 8752668, DOI: 10.1111/1523-1747.ep12348972.Peer-Reviewed Original ResearchConceptsTranscription factorsFibroblast growth factorBasic fibroblast growth factorMelanocyte-specific genesMelanogenic gene expressionTranscription factor microphthalmiaDownregulated transcription factorsDNA consensus siteTyrosinase-related protein 1Human metastatic melanoma cellsImmortalized mouse melanocytesPink-eyed dilutionCloudman S91 mouse melanomaMetastatic melanoma cellsSequestration of p300Transcriptional adaptorGrowth factorE1A mutantsConsensus sitesMouse melanocytesRegulatory proteinsMolecular basisOncogene RasGene expressionTumorigenic transformation
1995
Mouse 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
KIT ligand (mast cell growth factor) inhibits the growth of KIT-expressing melanoma cells.
Zakut R, Perlis R, Eliyahu S, Yarden Y, Givol D, Lyman S, Halaban R. KIT ligand (mast cell growth factor) inhibits the growth of KIT-expressing melanoma cells. Oncogene 1993, 8: 2221-9. PMID: 7687762.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell DivisionHematopoietic Cell Growth FactorsHumansMelanomaMolecular Sequence DataNeoplasm ProteinsPhosphorylationProtein-Tyrosine KinasesProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins c-kitRNA, MessengerRNA, NeoplasmStem Cell FactorTumor Cells, CulturedConceptsMast cell growth factorMelanoma cell linesNormal melanocyte developmentMelanoma cellsAberrant signal transductionMetastatic melanoma cell linesCell linesActivation of KITMelanocyte developmentSignal transductionKIT proto-oncogeneKinase activationKIT mRNAKit ligandNormal melanocytesProto-oncogeneKIT kinaseCell growth factorBiological responsesGrowth factorHuman melanomaMelanocytesCellsKIT expressionNeoplastic melanocytesA transcriptional inhibitor induced in human melanoma cells upon ultraviolet irradiation.
Yang Y, Rutberg S, Luo F, Spratt T, Halaban R, Ferrone S, Ronai Z. A transcriptional inhibitor induced in human melanoma cells upon ultraviolet irradiation. Molecular Cancer Research 1993, 4: 595-602. PMID: 8398900.Peer-Reviewed Original ResearchAltered 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 cellsMolecular analyses of a tyrosinase-negative albino family.
Park K, Chintamaneni C, Halaban R, Witkop C, Kwon B. Molecular analyses of a tyrosinase-negative albino family. American Journal Of Human Genetics 1993, 52: 406-13. PMID: 8430701, PMCID: PMC1682201.Peer-Reviewed Original ResearchMeSH KeywordsAlbinism, OculocutaneousBase SequenceBlotting, NorthernBlotting, SouthernChildDNA Mutational AnalysisElectrophoresis, Polyacrylamide GelFemaleFrameshift MutationGene LibraryGlycosylationHumansMaleMelanocytesMolecular Sequence DataMonophenol MonooxygenaseMutationPedigreePoint MutationPolymerase Chain ReactionPrecipitin TestsSequence DeletionConceptsAmino acid changesAcid changesPutative amino acid changesPremature termination signalTwo-nucleotide deletionSingle base substitutionTermination signalGel electrophoretic analysisN-glycosylationCDNA libraryBase pair deletionCodon 355Genomic DNAHomologous allelesNucleotide substitutionsSequence analysisMolecular analysisMissense mutationsTwo-base deletionExon 1Electrophoretic analysisCodon 226Exon 3AllelesTyrosinase-negative oculocutaneous albinismWhite mutants in mice shedding light on humans.
Halaban R, Moellmann G. White mutants in mice shedding light on humans. Journal Of Investigative Dermatology 1993, 100: 176s-185s. PMID: 8433006, DOI: 10.1038/jid.1993.10.Peer-Reviewed Original ResearchMeSH KeywordsAlbinismAmino Acid SequenceAnimalsBase SequenceHumansMiceMice, Inbred BALB CMice, Mutant StrainsMolecular Sequence DataPiebaldismPigmentation DisordersVitiligoConceptsMembrane receptor tyrosine kinasesMouse mutant modelsPink-eyed dilutionDefective signal transductionReceptor kinase activityEnzyme activityC-kitDistinct enzyme activitiesIdentification of mutationsRespective enzyme activitiesPiebald phenotypeShares homologyLocus proteinSignal transductionKinase activityCatalase BMolecular geneticsTyrosine kinaseWhite mutantsMutant modelsHair melanocytesDopachrome tautomerasePoint mutationsTyrosinase-negative albinismNormal pigmentation
1992
Scatter factor and hepatocyte growth factor: activities, properties, and mechanism.
Bhargava M, Joseph A, Knesel J, Halaban R, Li Y, Pang S, Goldberg I, Setter E, Donovan M, Zarnegar R. Scatter factor and hepatocyte growth factor: activities, properties, and mechanism. Molecular Cancer Research 1992, 3: 11-20. PMID: 1534687.Peer-Reviewed Original ResearchConceptsHepatocyte growth factorScatter factorPartial amino acid sequence dataAmino acid sequence dataAmino acid sequenceFibroblast-derived proteinHuman smooth muscle cellsVascular endothelial cell typesEndothelial cell typesGrowth factorSignificant homologyPosttranslational modificationsSequence dataRapid phosphorylationAcid sequenceBiological activityTyrosine residuesProtein productsCohesive coloniesCommon antigenic determinantsCell typesSpecies-related differencesProteinSerum-derived proteinsHuman hepatocyte growth factor
1991
A single base insertion in the putative transmembrane domain of the tyrosinase gene as a cause for tyrosinase-negative oculocutaneous albinism.
Chintamaneni C, Halaban R, Kobayashi Y, Witkop C, Kwon B. A single base insertion in the putative transmembrane domain of the tyrosinase gene as a cause for tyrosinase-negative oculocutaneous albinism. Proceedings Of The National Academy Of Sciences Of The United States Of America 1991, 88: 5272-5276. PMID: 1711223, PMCID: PMC51854, DOI: 10.1073/pnas.88.12.5272.Peer-Reviewed Original Research
1990
Recent Advances in the Molecular Biology of Pigmentation: Mouse Models
Halaban R, Moellmann G. Recent Advances in the Molecular Biology of Pigmentation: Mouse Models. Pigment Cell & Melanoma Research 1990, 3: 67-78. PMID: 1409441, DOI: 10.1111/j.1600-0749.1990.tb00352.x.Peer-Reviewed Original Research
1989
Isolation, Chromosomal Mapping, and Expression of the Mouse Tyrosinase Gene
Kwon B, Haq A, Wakulchik M, Kestler D, Barton D, Francke U, Lamoreux M, Whitney J, Halaban R. Isolation, Chromosomal Mapping, and Expression of the Mouse Tyrosinase Gene. Journal Of Investigative Dermatology 1989, 93: 589-594. PMID: 2507645, DOI: 10.1111/1523-1747.ep12319693.Peer-Reviewed Original ResearchConceptsMouse tyrosinaseTyrosinase geneMouse chromosome 7Mouse tyrosinase geneSomatic cell hybridsSouthern blot analysisChromosomal mappingGenomic clonesCell hybridsPromoter sequencesTATA elementAlbino locusChromosome 7Melanoma cell linesCDNA probeNormal melanocytesTyrosinase mRNABackcross miceBlot analysisFarthest upstreamCell linesDeletion miceGenesLociCloudman SMolecular basis of mouse Himalayan mutation
Kwon B, Halaban R, Chintamaneni C. Molecular basis of mouse Himalayan mutation. Biochemical And Biophysical Research Communications 1989, 161: 252-260. PMID: 2567165, DOI: 10.1016/0006-291x(89)91588-x.Peer-Reviewed Original ResearchConceptsAmino acid 420Histidine residuesAmino acidsTemperature-sensitive tyrosinaseCDNA libraryHimalayan miceMouse tyrosinaseInteresting mutantsNucleotide sequenceB proteinMolecular basisTyrosinase geneTyrosinase cDNAArginine residuesTyrosinase moleculesHuman tyrosinaseG changeResiduesMutationsTyrosinaseMutantsCDNAGenesMiceTyrosinase inhibitors
1988
Sequence analysis of mouse tyrosinase cDNA and the effect of melanotropin on its gene expression
Kwon B, Wakulchik M, Haq A, Halaban R, Kestler D. Sequence analysis of mouse tyrosinase cDNA and the effect of melanotropin on its gene expression. Biochemical And Biophysical Research Communications 1988, 153: 1301-1309. PMID: 3134020, DOI: 10.1016/s0006-291x(88)81370-6.Peer-Reviewed Original ResearchConceptsAmino acid sequenceAcid sequenceTyrosinase cDNAPotential N-glycosylation sitesMouse genomic cloneHistidine-rich regionMouse tyrosinase geneN-glycosylation sitesLevels of transcriptsCopper-binding siteMouse tyrosinase cDNADeduced proteinGenomic clonesTransmembrane sequenceHuman tyrosinase cDNACDNA clonesMouse tyrosinaseTyrosinase geneGene expressionSequence analysisAmino acidsHuman tyrosinaseClonesCDNAMelanoma cells
1987
Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus.
Kwon BS, Haq AK, Pomerantz SH, Halaban R. Isolation and sequence of a cDNA clone for human tyrosinase that maps at the mouse c-albino locus. Proceedings Of The National Academy Of Sciences Of The United States Of America 1987, 84: 7473-7477. PMID: 2823263, PMCID: PMC299318, DOI: 10.1073/pnas.84.21.7473.Peer-Reviewed Original ResearchConceptsCDNA clonesMelanocyte cDNA libraryRelated mRNA speciesHuman tyrosinaseAmino acid sequenceSouthern blot analysisStructural geneCDNA libraryNucleotide sequenceMRNA speciesAcid sequenceGlycosylation sitesCDNA insertDeletion mutationsCell typesAmino acidsCopper bindingBlot analysisClonesMalignant melanocytesLociSequenceTyrosinaseApproximate lengthKilobases