2017
Two transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation
Karabadzhak AG, Petti LM, Barrera FN, Edwards APB, Moya-Rodríguez A, Polikanov YS, Freites JA, Tobias DJ, Engelman DM, DiMaio D. Two transmembrane dimers of the bovine papillomavirus E5 oncoprotein clamp the PDGF β receptor in an active dimeric conformation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e7262-e7271. PMID: 28808001, PMCID: PMC5584431, DOI: 10.1073/pnas.1705622114.Peer-Reviewed Original ResearchConceptsTransmembrane domainE5 proteinE5 dimerPlatelet-derived growth factor β receptorGrowth factor β receptorActive dimeric conformationPDGF β-receptorTransmembrane dimerProtein bindsMembrane environmentReceptor dimerizationDimeric conformationAtom molecular dynamics simulationsBiochemical experimentsMouse cellsMolecular mechanismsActive dimerΒ receptorBovine papillomavirusProteinSpecific interactionsMembrane modelingReceptor activationDimerizationComplexes
2001
Mechanisms of cell transformation by papillomavirus E5 proteins
DiMaio D, Mattoon D. Mechanisms of cell transformation by papillomavirus E5 proteins. Oncogene 2001, 20: 7866-7873. PMID: 11753669, DOI: 10.1038/sj.onc.1204915.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBovine papillomavirus 1Cell Transformation, ViralErbB ReceptorsOncogene Proteins, ViralReceptor, Platelet-Derived Growth Factor betaVacuolar Proton-Translocating ATPasesConceptsE5 proteinBovine papillomavirus E5 proteinCellular signal transduction pathwaysSignal transduction pathwaysLigand-independent fashionGrowth factor receptor activityReceptor tyrosine kinasesTransforming proteinTransduction pathwaysGrowth factor receptorVacuolar ATPaseReceptor dimerizationTyrosine kinaseCell transformationProteinViral transformationBovine papillomavirusFactor receptorUnique mechanismStable complexesNew insightsReceptor activityPathwayReceptorsKinase
2000
The platelet-derived growth factor ß receptor as a target of the bovine papillomavirus E5 protein
DiMaio D, Lai C, Mattoon D. The platelet-derived growth factor ß receptor as a target of the bovine papillomavirus E5 protein. Cytokine & Growth Factor Reviews 2000, 11: 283-293. PMID: 10959076, DOI: 10.1016/s1359-6101(00)00012-5.Peer-Reviewed Original ResearchConceptsE5 proteinBovine papillomavirus E5 proteinSH2 domain-containing proteinsCellular signal transduction pathwaysDomain-containing proteinsSignal transduction complexSignal transduction pathwaysLigand-independent fashionGrowth factor receptor activitySpecific transmembraneTransduction complexCytoplasmic domainTransmembrane proteinTransduction pathwaysReceptor dimerizationTyrosine residuesAmino acidsProteinViral transformationDirect interactionBovine papillomavirusUnique mechanismStable complexesComplex formationNew insightsE2F-Rb Complexes Assemble and Inhibit cdc25A Transcription in Cervical Carcinoma Cells following Repression of Human Papillomavirus Oncogene Expression
Wu L, Goodwin E, Naeger L, Vigo E, Galaktionov K, Helin K, DiMaio D. E2F-Rb Complexes Assemble and Inhibit cdc25A Transcription in Cervical Carcinoma Cells following Repression of Human Papillomavirus Oncogene Expression. Molecular And Cellular Biology 2000, 20: 7059-7067. PMID: 10982822, PMCID: PMC86242, DOI: 10.1128/mcb.20.19.7059-7067.2000.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesBovine papillomavirus 1Carcinoma, Squamous CellCarrier ProteinsCdc25 PhosphatasesCell CycleCell Cycle ProteinsCell Transformation, NeoplasticCell Transformation, ViralConsensus SequenceCysteine EndopeptidasesDNA, NeoplasmDNA-Binding ProteinsE2F Transcription FactorsE2F4 Transcription FactorFemaleGene Expression Regulation, NeoplasticGene Expression Regulation, ViralGenes, RetinoblastomaHumansMacromolecular SubstancesMultienzyme ComplexesNeoplasm ProteinsPapillomaviridaePapillomavirus InfectionsPhosphoproteinsPromoter Regions, GeneticProteasome Endopeptidase ComplexProtein BindingProteinsRecombinant Fusion ProteinsRetinoblastoma ProteinRetinoblastoma-Binding Protein 1Retinoblastoma-Like Protein p130Transcription Factor DP1Transcription FactorsTransfectionTumor Cells, CulturedTumor Virus InfectionsUterine Cervical NeoplasmsViral ProteinsConceptsCdc25A promoterE6/E7 repressionCervical carcinoma cellsE2F siteBovine papillomavirus E2 proteinE2 proteinE7 repressionWild-type E2 proteinE2F-responsive promotersRb tumor suppressor pathwayPapillomavirus E2 proteinCarcinoma cellsE2F-Rb complexesCell cycle genesHuman papillomavirus oncogene expressionHuman papillomavirus (HPV) E6/E7 oncogenesTumor suppressor pathwayMechanism of repressionHPV E6/E7 expressionCell cycle progressionCdc25A transcriptionDramatic growth arrestE2F complexesConsensus E2FProtein complexesBovine Papillomavirus E5 Protein Induces the Formation of Signal Transduction Complexes Containing Dimeric Activated Platelet-derived Growth Factor β Receptor and Associated Signaling Proteins*
Lai C, Henningson C, DiMaio D. Bovine Papillomavirus E5 Protein Induces the Formation of Signal Transduction Complexes Containing Dimeric Activated Platelet-derived Growth Factor β Receptor and Associated Signaling Proteins*. Journal Of Biological Chemistry 2000, 275: 9832-9840. PMID: 10734138, DOI: 10.1074/jbc.275.13.9832.Peer-Reviewed Original ResearchMeSH KeywordsBovine papillomavirus 1Cell LineCell Transformation, ViralDimerizationOncogene Proteins, ViralPrecipitin TestsReceptor, Platelet-Derived Growth Factor betaSignal TransductionConceptsBovine papillomavirus E5 proteinE5 proteinPDGF beta receptorBeta receptor complexCellular platelet-derived growth factor (PDGF) beta receptorReceptor complexPlatelet-derived growth factor beta receptorPlatelet-derived growth factor β receptorRas-GTPase activating proteinAssembly of multiproteinSignal transduction complexGrowth factor β receptorGrowth factor beta receptorCell growth transformationTransduction complexBeta receptorsP85 subunitSignaling proteinsPhospholipase CgammaActivating proteinReceptor dimersConstitutive activationInactive receptorProteinReceptor molecules
1999
The Bovine Papillomavirus E5 Protein Requires a Juxtamembrane Negative Charge for Activation of the Platelet-Derived Growth Factor β Receptor and Transformation of C127 Cells
Klein O, Kegler-Ebo D, Su J, Smith S, DiMaio D. The Bovine Papillomavirus E5 Protein Requires a Juxtamembrane Negative Charge for Activation of the Platelet-Derived Growth Factor β Receptor and Transformation of C127 Cells. Journal Of Virology 1999, 73: 3264-3272. PMID: 10074180, PMCID: PMC104090, DOI: 10.1128/jvi.73.4.3264-3272.1999.Peer-Reviewed Original ResearchConceptsPlatelet-derived growth factor beta receptorPDGF beta receptorGrowth factor beta receptorE5 proteinBovine papillomavirus E5 proteinCell transformationHomodimeric transmembrane proteinSustained receptor activationC127 mouse fibroblastsExtracellular juxtamembrane regionBeta receptorsE5 dimerE5 mutantsDouble mutantJuxtamembrane regionTransmembrane proteinC127 cellsC-terminusAcidic residuesE5 geneMutantsPosition 33Mouse fibroblastsProteinSalt bridge
1998
Role of Glutamine 17 of the Bovine Papillomavirus E5 Protein in Platelet-Derived Growth Factor β Receptor Activation and Cell Transformation
Klein O, Polack G, Surti T, Kegler-Ebo D, Smith S, DiMaio D. Role of Glutamine 17 of the Bovine Papillomavirus E5 Protein in Platelet-Derived Growth Factor β Receptor Activation and Cell Transformation. Journal Of Virology 1998, 72: 8921-8932. PMID: 9765437, PMCID: PMC110309, DOI: 10.1128/jvi.72.11.8921-8932.1998.Peer-Reviewed Original ResearchConceptsBovine papillomavirus E5 proteinPDGF beta receptorE5 proteinTransform cellsCellular platelet-derived growth factor (PDGF) beta receptorAmino acidsBa/F3 hematopoietic cellsPosition 17Cell transformationPlatelet-derived growth factor beta receptorHomodimeric transmembrane proteinReceptor tyrosine phosphorylationGrowth factor beta receptorReceptor tyrosine kinasesPDGF receptor tyrosine kinaseReceptor activationPossible amino acidsBeta receptorsStable complexesComplex formationMutant proteinsTransmembrane domainTransmembrane proteinGrowth factor-beta (TGF-beta) receptor activationTyrosine phosphorylationVIROCRINE TRANSFORMATION: The Intersection Between Viral Transforming Proteins and Cellular Signal Transduction Pathways
DiMaio D, Lai C, Klein O. VIROCRINE TRANSFORMATION: The Intersection Between Viral Transforming Proteins and Cellular Signal Transduction Pathways. Annual Review Of Microbiology 1998, 52: 397-421. PMID: 9891803, DOI: 10.1146/annurev.micro.52.1.397.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Polyomavirus TransformingBovine papillomavirus 1CattleCell Transformation, ViralHerpesvirus 4, HumanMiceOncogene ProteinsReceptor Protein-Tyrosine KinasesReceptor, Platelet-Derived Growth Factor betaReceptors, ErythropoietinReceptors, Platelet-Derived Growth FactorReceptors, Tumor Necrosis FactorSignal TransductionViral Envelope ProteinsViral Matrix ProteinsViral ProteinsConceptsCellular signal transduction pathwaysSignal transduction pathwaysTransduction pathwaysPlatelet-derived growth factor beta receptorPolyoma virus middle T antigenCellular signal transductionViral transforming proteinsCellular signaling pathwaysViral transformationMiddle T antigenGrowth factor beta receptorReceptor tyrosine kinasesTransforming proteinSignal transductionE5 proteinTumor necrosis factor receptorErythropoietin receptorTyrosine kinaseSignaling pathwaysCell transformationDiverse virusesNecrosis factor receptorViral oncoproteinsSpleen focusT antigen
1997
Virocrine transformation
Drummond-Barbosa D, DiMaio D. Virocrine transformation. Biochimica Et Biophysica Acta 1997, 1332: m1-m17. PMID: 9061007, DOI: 10.1016/s0304-419x(96)00034-0.Peer-Reviewed Original ResearchAntigens, Viral, TumorCell Transformation, ViralGrowth SubstancesOncogene Proteins, ViralPhosphorylationReceptor Protein-Tyrosine KinasesReceptor, IGF Type 1Receptor, Platelet-Derived Growth Factor betaReceptors, ErythropoietinReceptors, Growth FactorReceptors, Platelet-Derived Growth FactorReceptors, Tumor Necrosis FactorSignal TransductionTerminology as TopicViral Envelope ProteinsViral Matrix ProteinsViral ProteinsVirus Replication
1995
The HPV16 E5 Protein: Expression, Detection, and Stable Complex Formation with Transmembrane Proteins in COS Cells
Hwang E, Nottoli T, Dimaio D. The HPV16 E5 Protein: Expression, Detection, and Stable Complex Formation with Transmembrane Proteins in COS Cells. Virology 1995, 211: 227-233. PMID: 7645215, DOI: 10.1006/viro.1995.1395.Peer-Reviewed Original ResearchConceptsE5 proteinHPV16 E5 proteinStable complex formationTransmembrane proteinGrowth factor receptorE5 genePlatelet-derived growth factor beta receptorViral proteinsVesicular stomatitis virus glycoproteinComplex formationFactor receptorCOS monkey cellsGrowth factor beta receptorStable growth transformationCultured cell systemsEpidermal growth factor receptorFactor 1 receptorTransforming proteinCoimmunoprecipitation analysisCOS cellsExpression vectorMonkey cellsBiochemical propertiesProteinE5 expressionAn intact PDGF signaling pathway is required for efficient growth transformation of mouse C127 cells by the bovine papillomavirus E5 protein.
Riese D, DiMaio D. An intact PDGF signaling pathway is required for efficient growth transformation of mouse C127 cells by the bovine papillomavirus E5 protein. Oncogene 1995, 10: 1431-9. PMID: 7731695.Peer-Reviewed Original ResearchConceptsBPV E5 proteinPDGF beta receptorE5 proteinE5 geneC127 cellsBovine papillomavirus E5 proteinPDGF beta-receptor genePlatelet-derived growth factor beta receptorGrowth transformationBovine papillomavirus type 1 E5 proteinC127 cell linesMembrane-associated proteinsMouse C127 cellsHeterologous cell typesV-sis oncogeneDNA synthesisGrowth factor beta receptorStable growth transformationBeta receptor geneCell linesBeta receptorsBPV E5Reduced DNA synthesisMouse C127Genetic support
1993
Hierarchy of polyadenylation site usage by bovine papillomavirus in transformed mouse cells
Andrews E, DiMaio D. Hierarchy of polyadenylation site usage by bovine papillomavirus in transformed mouse cells. Journal Of Virology 1993, 67: 7705-7710. PMID: 7901430, PMCID: PMC238246, DOI: 10.1128/jvi.67.12.7705-7710.1993.Peer-Reviewed Original ResearchAnimalsAntisense Elements (Genetics)Base SequenceBovine papillomavirus 1Cell Transformation, ViralCells, CulturedCloning, MolecularConsensus SequenceDNA, ComplementaryMiceMolecular Sequence DataMutagenesisPoly APolymerase Chain ReactionRegulatory Sequences, Nucleic AcidRNA Processing, Post-TranscriptionalRNA, MessengerSequence Analysis, DNAPlatelet-derived growth factor receptor can mediate tumorigenic transformation by the bovine papillomavirus E5 protein.
Nilson L, DiMaio D. Platelet-derived growth factor receptor can mediate tumorigenic transformation by the bovine papillomavirus E5 protein. Molecular And Cellular Biology 1993, 13: 4137-4145. PMID: 8321218, PMCID: PMC359963, DOI: 10.1128/mcb.13.7.4137.Peer-Reviewed Original ResearchConceptsE5 proteinPDGF receptorPlatelet-derived growth factorBovine papillomavirus E5 proteinTumorigenic transformationMouse mammary gland cellsMurine mammary epithelial cell lineBovine papillomavirus type 1 E5 proteinPDGF receptor genesBPV E5 proteinMammary epithelial cell lineSustained proliferative signalEpidermal growth factor receptor (EGFR) pathwayPlatelet-derived growth factor receptorMammary gland cellsStable complexesGrowth factor receptor pathwayPDGF beta receptorTransforming proteinNMuMG cellsCellular proteinsGrowth factor receptorTyrosine phosphorylationEpithelial cell lineFibroblast transformation
1992
Stable association between the bovine papillomavirus E5 transforming protein and activated platelet-derived growth factor receptor in transformed mouse cells.
Petti L, DiMaio D. Stable association between the bovine papillomavirus E5 transforming protein and activated platelet-derived growth factor receptor in transformed mouse cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1992, 89: 6736-6740. PMID: 1323117, PMCID: PMC49578, DOI: 10.1073/pnas.89.15.6736.Peer-Reviewed Original ResearchConceptsE5 proteinPlatelet-derived growth factorGrowth factor receptor activationPDGF receptorMouse C127 cellsBovine papillomavirus E5Platelet-derived growth factor receptorShorter proteinTransforming proteinCoimmunoprecipitation analysisGrowth factor receptorReceptor transmitsStable associationC127 cellsTumorigenic transformationMouse cellsProteinBovine papillomavirusFactor receptorDistinct mechanismsStable complexesGrowth factorReceptor activationImportant targetBeta receptorsA glutamine residue in the membrane-associating domain of the bovine papillomavirus type 1 E5 oncoprotein mediates its binding to a transmembrane component of the vacuolar H(+)-ATPase
Goldstein D, Kulke R, Dimaio D, Schlegel R. A glutamine residue in the membrane-associating domain of the bovine papillomavirus type 1 E5 oncoprotein mediates its binding to a transmembrane component of the vacuolar H(+)-ATPase. Journal Of Virology 1992, 66: 405-413. PMID: 1370089, PMCID: PMC238300, DOI: 10.1128/jvi.66.1.405-413.1992.Peer-Reviewed Original ResearchConceptsK proteinGrowth factor receptorE5 oncoproteinGlutamine residuesRandom hydrophobic sequencesSpecific amino acid residuesMembrane-associated domainMajor transforming proteinK protein componentCarboxyl-terminal domainEndoplasmic reticulum membraneFactor receptorBovine papillomavirus type 1Colony-stimulating factor 1 receptorTransformation-defective mutantsAmino acid residuesPotential binding sitesPlatelet-derived growth factor receptorAmino acid substitutionsPapillomavirus type 1Hydrophilic amino acidsE5 dimerE5 mutantsFactor 1 receptorProtein complexesThe central hydrophobic domain of the bovine papillomavirus E5 transforming protein can be functionally replaced by many hydrophobic amino acid sequences containing a glutamine
Kulke R, Horwitz B, Zibello T, DiMaio D. The central hydrophobic domain of the bovine papillomavirus E5 transforming protein can be functionally replaced by many hydrophobic amino acid sequences containing a glutamine. Journal Of Virology 1992, 66: 505-511. PMID: 1727496, PMCID: PMC238311, DOI: 10.1128/jvi.66.1.505-511.1992.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell LineCell Transformation, NeoplasticCell Transformation, ViralDNAGlutamineMolecular Sequence DataOncogene Proteins, ViralPrecipitin TestsConceptsHydrophobic amino acidsAmino acidsE5 proteinRandom hydrophobic sequencesHydrophobic domainRodent fibroblast cell linesCentral hydrophobic domainHydrophobic amino acid sequenceCarboxyl-terminal amino acidsMouse C127 cellsAmino acid sequenceClasses of mutantsAbsence of glutamineBovine papillomavirus E5Mutant proteinsTransforming proteinDefective mutantsHydrophobic sequenceFibroblast cell lineProtein stabilityAcid sequenceC127 cellsHomodimer formationEfficient transformationProtein
1991
Biological properties of the deer papillomavirus E5 gene in mouse C127 cells: growth transformation, induction of DNA synthesis, and activation of the platelet-derived growth factor receptor
Kulke R, DiMaio D. Biological properties of the deer papillomavirus E5 gene in mouse C127 cells: growth transformation, induction of DNA synthesis, and activation of the platelet-derived growth factor receptor. Journal Of Virology 1991, 65: 4943-4949. PMID: 1651413, PMCID: PMC248956, DOI: 10.1128/jvi.65.9.4943-4949.1991.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBlotting, NorthernCell Transformation, ViralCloning, MolecularDeerDNAGene ExpressionGenes, ViralIn Vitro TechniquesMiceMolecular Sequence DataOncogene Proteins, ViralPapillomaviridaePlatelet-Derived Growth FactorReceptors, Cell SurfaceReceptors, Platelet-Derived Growth FactorRNA, ViralViral Structural ProteinsConceptsMouse C127 cellsE5 proteinC127 cellsE5 genePlatelet-derived growth factor beta receptorPDGF receptorBovine papillomavirus type 1 E5 proteinConstitutive tyrosine phosphorylationDNA synthesisGrowth factor beta receptorBovine papillomavirus type 1Platelet-derived growth factor receptorTransformation of fibroblastsPapillomavirus type 1Sequence similarityGrowth factor receptorTyrosine phosphorylationBiological activityShort regionFoci formationProteinFactor receptorReceptor formsB chainGrowth transformationTransforming Activity of Bovine and Human Papillomaviruses in Cultured Cells
DiMaio D. Transforming Activity of Bovine and Human Papillomaviruses in Cultured Cells. Advances In Cancer Research 1991, 56: 133-159. PMID: 1851373, DOI: 10.1016/s0065-230x(08)60480-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBovine papillomavirus 1CattleCell Transformation, NeoplasticCell Transformation, ViralCells, CulturedHumansPapillomaviridaeConceptsBovine papillomavirus type ICultured cellsTransient expression systemViral gene productsGene productsComplex phenotypesExpression systemTumorigenic transformationBiochemical eventsMolecular descriptionCell morphologyCottontail rabbit papillomavirusBiological responsesHuman carcinomasCultured fibroblastsGrowth propertiesCellsRabbit papillomavirusHomogeneous populationProfound effectGenesType ISimilar activityTumorigenesisPhenotype
1989
Open reading frames E6 and E7 of bovine papillomavirus type 1 are both required for full transformation of mouse C127 cells
Neary K, DiMaio D. Open reading frames E6 and E7 of bovine papillomavirus type 1 are both required for full transformation of mouse C127 cells. Journal Of Virology 1989, 63: 259-266. PMID: 2535732, PMCID: PMC247680, DOI: 10.1128/jvi.63.1.259-266.1989.Peer-Reviewed Original ResearchConceptsBovine papillomavirus type 1Open reading frames E6Mouse C127 cellsFull-length viral genomesAnchorage-independent growthPapillomavirus type 1Focus-forming activityC127 cellsORF E6First methionine codonViral genomeColony formationRetrovirus long terminal repeatsSeries of mutationsE6/E7Second ATG codonLong terminal repeatBPV1 genomeMethionine codonATG codonNumber plasmidE5 geneSpecific proteinsSimultaneous disruptionE6 protein
1988
44-amino-acid E5 transforming protein of bovine papillomavirus requires a hydrophobic core and specific carboxyl-terminal amino acids.
Horwitz B, Burkhardt A, Schlegel R, DiMaio D. 44-amino-acid E5 transforming protein of bovine papillomavirus requires a hydrophobic core and specific carboxyl-terminal amino acids. Molecular And Cellular Biology 1988, 8: 4071-4078. PMID: 2847028, PMCID: PMC365476, DOI: 10.1128/mcb.8.10.4071.Peer-Reviewed Original ResearchConceptsAmino acid substitutionsE5 proteinAmino acidsTransforming proteinAcid substitutionsCarboxyl-terminal thirdCarboxyl-terminal amino acidsCharacterization of mutantsSpecific amino acid sequencesMouse C127 cellsAmino acid sequenceBovine papillomavirus type 1Specific amino acidsHydrophobic amino acidsPapillomavirus type 1Focus-forming activityCysteine residuesAcid sequenceC127 cellsSaturation mutagenesisE5 geneTransforming activityEssential amino acidsFoci formationMissense mutations