2020
Cell-penetrating peptide inhibits retromer-mediated human papillomavirus trafficking during virus entry
Zhang P, Moreno R, Lambert PF, DiMaio D. Cell-penetrating peptide inhibits retromer-mediated human papillomavirus trafficking during virus entry. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 6121-6128. PMID: 32123072, PMCID: PMC7084110, DOI: 10.1073/pnas.1917748117.Peer-Reviewed Original ResearchConceptsEssential protein-protein interactionsCellular protein complexesProtein-protein interactionsIntracellular virus traffickingRetrograde transport pathwaySites of replicationCell-penetrating sequenceProtein complexesCellular proteinsVirus replicationHPV16 pseudovirus infectionVirus traffickingL2 capsid proteinsAspects of infectionCapsid proteinHPV entryViral genomeViral proteinsIncoming virionsViral componentsHuman papillomavirus infectionProteinAntiviral targetDose-dependent blockVirus entry
2019
Introduction
Enquist L, Dermody T, DiMaio D. Introduction. Annual Review Of Virology 2019, 6: 1-2. PMID: 31567061, DOI: 10.1146/annurev-vi-06-072619-100001.Peer-Reviewed Original Research
2017
Single methyl groups can act as toggle switches to specify transmembrane Protein-protein interactions
He L, Steinocher H, Shelar A, Cohen EB, Heim EN, Kragelund BB, Grigoryan G, DiMaio D. Single methyl groups can act as toggle switches to specify transmembrane Protein-protein interactions. ELife 2017, 6: e27701. PMID: 28869036, PMCID: PMC5597333, DOI: 10.7554/elife.27701.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsErythropoietin receptorTransmembrane proteinTransmembrane protein-protein interactionsTMD interactionsModel transmembrane proteinMouse erythropoietin receptorHuman erythropoietin receptorSingle methyl groupGrowth factor independenceSide chain methyl groupsCellular processesMouse cellsFactor independenceChain methyl groupsIntrinsic specificityToggle switchTraptamersMethyl groupProteinReceptor activitySpecific positionsReceptorsSpecificityOligomerizationTwo 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
2016
An Update on Canine, Feline and Bovine Papillomaviruses
da Costa R, Peleteiro M, Pires M, DiMaio D. An Update on Canine, Feline and Bovine Papillomaviruses. Transboundary And Emerging Diseases 2016, 64: 1371-1379. PMID: 27615361, DOI: 10.1111/tbed.12555.Peer-Reviewed Original ResearchConceptsAnimal healthSignificant economic lossesNumber of papillomavirusesCross-species infectionFarm animalsVeterinary practitionersNew viral typesEconomic lossesWild animalsWorldwide importanceFeline papillomavirusesAnimal papillomavirusesPrevalent pathogenDomestic catsPapillomavirus researchCell biologyFascinating modelAnimalsBovine papillomavirusRecent discoveryGreat impactPathogensFelineCanineWide range
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 ResearchConceptsE5 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 activityPathwayReceptorsKinaseIdentification of the transmembrane dimer interface of the bovine papillomavirus E5 protein
Mattoon D, Gupta K, Doyon J, Loll P, DiMaio D. Identification of the transmembrane dimer interface of the bovine papillomavirus E5 protein. Oncogene 2001, 20: 3824-3834. PMID: 11439346, DOI: 10.1038/sj.onc.1204523.Peer-Reviewed Original ResearchConceptsBovine papillomavirus E5 proteinE5 proteinDimer interfacePlatelet-derived growth factor β receptorEssential glutamine residueHeterologous dimerization domainGrowth factor β receptorNon-productive interactionsReceptor tyrosine phosphorylationFocus formation assayPDGF β-receptorDimerization domainHomodimeric proteinTyrosine phosphorylationGenetic methodsGlutamine residuesActive chimerasΒ receptorActive orientationFormation assaysProtein helicesProteinPosition 17ReceptorsPhosphorylation
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 insightsRepression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways
Goodwin E, DiMaio D. Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 12513-12518. PMID: 11070078, PMCID: PMC18795, DOI: 10.1073/pnas.97.23.12513.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBovine papillomavirus 1Carrier ProteinsCattleCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p21CyclinsDNADNA-Binding ProteinsE2F Transcription FactorsFemaleGene Expression Regulation, ViralGenes, Tumor SuppressorHeLa CellsHumansNuclear ProteinsOncogene Proteins, ViralOncogenesPapillomaviridaePapillomavirus E7 ProteinsPhosphoproteinsProteinsProto-Oncogene ProteinsProto-Oncogene Proteins c-mdm2Repressor ProteinsRetinoblastoma ProteinRetinoblastoma-Binding Protein 1Retinoblastoma-Like Protein p107Retinoblastoma-Like Protein p130Signal TransductionTranscription Factor DP1Transcription FactorsTumor Suppressor Protein p53Uterine Cervical NeoplasmsViral ProteinsConceptsTumor suppressor pathwayE6/E7 repressionPosttranscriptional inductionSuppressor pathwayBovine papillomavirus E2 proteinE7 repressionCyclin-dependent kinase activityHeLa cellsE2F-regulated genesE2F-responsive genesRb tumor suppressor pathwayPapillomavirus E2 proteinCell cycle machineryE2 proteinHPV16 E6/E7 genesHeLa cervical carcinoma cellsP53-responsive genesTumor suppressor functionHPV E6Growth inhibitory signalsE6/E7 genesRapid repressionCellular DNA synthesisCycle machineryHuman papillomavirus oncogenesRapid induction of senescence in human cervical carcinoma cells
Goodwin E, Yang E, Lee C, Lee H, DiMaio D, Hwang E. Rapid induction of senescence in human cervical carcinoma cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 10978-10983. PMID: 11005870, PMCID: PMC27134, DOI: 10.1073/pnas.97.20.10978.Peer-Reviewed Original ResearchConceptsHuman papillomavirus E6Cervical carcinoma cellsCarcinoma cellsPapillomavirus E6Cervical carcinoma cell linesCell cycle regulatory proteinsViral oncogene expressionHuman cervical carcinoma cell lineCarcinoma cell linesCycle regulatory proteinsHuman cervical carcinoma cellsE7 oncogenesE7 proteinTransient alterationsCancer cellsOncogene expressionHuman cancersPhenotypic markersTelomerase activityCell linesRegulatory proteinsRapid inductionSenescence pathwaysCellsE2 regulatory protein
1999
Bovine papillomavirus E2 protein activates a complex growth-inhibitory program in p53-negative HT-3 cervical carcinoma cells that includes repression of cyclin A and cdc25A phosphatase genes and accumulation of hypophosphorylated retinoblastoma protein.
Naeger L, Goodwin E, Hwang E, DeFilippis R, Zhang H, DiMaio D. Bovine papillomavirus E2 protein activates a complex growth-inhibitory program in p53-negative HT-3 cervical carcinoma cells that includes repression of cyclin A and cdc25A phosphatase genes and accumulation of hypophosphorylated retinoblastoma protein. Molecular Cancer Research 1999, 10: 413-22. PMID: 10392903.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCattleCDC2-CDC28 KinasesCdc25 PhosphatasesCell Cycle ProteinsCell DivisionCyclin ACyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclinsDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorEnzyme InhibitorsFemaleGene Expression RegulationGrowth InhibitorsHeLa CellsHumansPhosphoprotein PhosphatasesPhosphorylationProtein Serine-Threonine KinasesProtein Tyrosine PhosphatasesRepressor ProteinsRetinoblastoma ProteinRetinoblastoma-Binding Protein 1Transcription Factor DP1Transcription FactorsTumor Cells, CulturedTumor Suppressor Protein p53Uterine Cervical NeoplasmsViral ProteinsConceptsCervical carcinoma cell linesHT-3 cellsCarcinoma cell linesE2 proteinE6/E7 genesCell linesGrowth inhibitionCervical carcinoma cellsCyclin ACyclin-dependent kinase 2 activityExpression of CDC25AKinase 2 activityE7 genesCell cycle componentsCarcinoma cellsCDC25B expressionE2 expressionProtein levelsThe 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 proteinC-terminusC127 cellsAcidic residuesE5 geneMutantsPosition 33Mouse fibroblastsProteinSalt bridge
1998
Bovine papillomavirus E5 protein induces oligomerization and trans-phosphorylation of the platelet-derived growth factor β receptor
Lai C, Henningson C, DiMaio D. Bovine papillomavirus E5 protein induces oligomerization and trans-phosphorylation of the platelet-derived growth factor β receptor. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 15241-15246. PMID: 9860953, PMCID: PMC28027, DOI: 10.1073/pnas.95.26.15241.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsBovine papillomavirus 1CattleCell LineCell Line, TransformedCross-Linking ReagentsDimerizationHumansKineticsMacromolecular SubstancesMiceOncogene Proteins, ViralPhosphorylationProtein-Tyrosine KinasesReceptor, Platelet-Derived Growth Factor betaReceptors, Platelet-Derived Growth FactorRecombinant ProteinsSequence DeletionTransfectionConceptsBovine papillomavirus E5 proteinE5 proteinPDGF beta receptorCellular platelet-derived growth factor (PDGF) beta receptorKinase-negative mutant receptorPlatelet-derived growth factor beta receptorPlatelet-derived growth factor β receptorChemical cross-linking experimentsGrowth factor β receptorConstitutive tyrosine phosphorylationGrowth factor beta receptorLigand-independent fashionCross-linking experimentsReceptor tyrosine kinasesStable complexesExtracts of cellsPDGF beta-receptor activationIntramolecular autophosphorylationBeta receptorsCoimmunoprecipitation experimentsTransmembrane proteinReceptor activationTyrosine phosphorylationReceptor dimerizationMutant receptorsA single amino acid substitution in a WW‐like domain of diverse members of the PDGF receptor subfamily of tyrosine kinases causes constitutive receptor activation
Irusta P, DiMaio D. A single amino acid substitution in a WW‐like domain of diverse members of the PDGF receptor subfamily of tyrosine kinases causes constitutive receptor activation. The EMBO Journal 1998, 17: 6912-6923. PMID: 9843497, PMCID: PMC1171039, DOI: 10.1093/emboj/17.23.6912.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmino Acid SequenceAmino Acid SubstitutionAnimalsBinding SitesCell Line, TransformedCloning, MolecularDimerizationEnzyme ActivationHumansInterleukin-3LigandsMiceMolecular Sequence DataMutagenesis, Site-DirectedPeptidesPhosphorylationPolymerase Chain ReactionReceptor Protein-Tyrosine KinasesReceptor, Platelet-Derived Growth Factor betaReceptors, Platelet-Derived Growth FactorSequence Homology, Amino AcidStructure-Activity RelationshipTyrosineValineConceptsTyrosine kinase activityKinase activityTyrosine kinasePlatelet-derived growth factor beta receptorCytoplasmic juxtamembrane domainPDGF receptorSignal transduction proteinsWW-like domainTransmembrane receptor tyrosine kinaseProtein-protein interactionsBa/F3 cellsGST fusion proteinSingle amino acid substitutionConstitutive receptor activationGrowth factor beta receptorAbsence of ligandReceptor tyrosine kinasesAmino acid substitutionsSequence PPXYTransduction proteinsWW domainsCellular functionsJuxtamembrane regionTyrosine phosphorylationAlanine substitutionsStructural models of the bovine papillomavirus E5 protein
Surti T, Klein O, Aschheim K, DiMaio D, Smith S. Structural models of the bovine papillomavirus E5 protein. Proteins Structure Function And Bioinformatics 1998, 33: 601-612. PMID: 9849943, DOI: 10.1002/(sici)1097-0134(19981201)33:4<601::aid-prot12>3.0.co;2-i.Peer-Reviewed Original ResearchConceptsBovine papillomavirus E5 proteinE5 dimerE5 proteinType II integral membrane proteinIntegral membrane proteinsPrevious mutagenesis studiesLigand-independent activationDisulfide-linked homodimerPDGF beta receptorMembrane proteinsTransmembrane orientationMutagenesis studiesMembrane bilayerCell transformationGenetic resultsProteinGln17Receptor moleculesMolecular scaffoldsComplex formationAsp33Computational searchDimerizationDimer structureDimersRole 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 antigenTransactivation-Competent Bovine Papillomavirus E2 Protein Is Specifically Required for Efficient Repression of Human Papillomavirus Oncogene Expression and for Acute Growth Inhibition of Cervical Carcinoma Cell Lines
Goodwin E, Naeger L, Breiding D, Androphy E, DiMaio D. Transactivation-Competent Bovine Papillomavirus E2 Protein Is Specifically Required for Efficient Repression of Human Papillomavirus Oncogene Expression and for Acute Growth Inhibition of Cervical Carcinoma Cell Lines. Journal Of Virology 1998, 72: 3925-3934. PMID: 9557678, PMCID: PMC109618, DOI: 10.1128/jvi.72.5.3925-3934.1998.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesBovine papillomavirus 1CattleCell DivisionCell NucleusCOS CellsDNADNA-Binding ProteinsFemaleGene Expression Regulation, ViralHeLa CellsHumansMutagenesisOncogene Proteins, ViralOncogenesPapillomaviridaeRepressor ProteinsRNA, MessengerRNA, ViralTrans-ActivatorsTranscriptional ActivationTumor Cells, CulturedUterine Cervical NeoplasmsViral ProteinsConceptsPapillomavirus E2 proteinGrowth arrestHT-3 cellsEfficient repressionTransactivation domainE2 proteinHeLa cellsG1/S-phase growth arrestE2 mutantsBovine papillomavirus type 1 E2 proteinBovine papillomavirus E2 proteinHerpes simplex virus VP16Reporter plasmidAcute growth inhibitionE2 transactivation domainGrowth inhibitionCervical carcinoma cell linesBPV1 E2 proteinCarcinoma cell linesHuman papillomavirus oncogene expressionViral DNA replicationPhase growth arrestSequence-specific transactivatorCell linesWild-type p53 geneOncogenic activation of the PDGF β receptor by the transmembrane domain of p185neu*
Petti L, Irusta P, DiMaio D. Oncogenic activation of the PDGF β receptor by the transmembrane domain of p185neu*. Oncogene 1998, 16: 843-851. PMID: 9484775, DOI: 10.1038/sj.onc.1201590.Peer-Reviewed Original ResearchConceptsBa/F3 cellsTransmembrane domainBa/F3 hematopoietic cellsF3 cellsWild-type PDGF receptorNovel tyrosine phosphorylated proteinsIL-3-independent growthTyrosine phosphorylated proteinsDistinct signaling pathwaysWild-type PDGFLevels of phosphotyrosineWild-type receptorIL-3Β receptorPDGF β-receptorPhosphorylated proteinsTyrosine autophosphorylationOncogenic formsKinase activityMouse C127Receptor homodimerizationOncogenic activationSignaling pathwaysChimeric receptorsFoci formation
1997
Identification of amino acids in the transmembrane and juxtamembrane domains of the platelet-derived growth factor receptor required for productive interaction with the bovine papillomavirus E5 protein
Petti L, Reddy V, Smith S, DiMaio D. Identification of amino acids in the transmembrane and juxtamembrane domains of the platelet-derived growth factor receptor required for productive interaction with the bovine papillomavirus E5 protein. Journal Of Virology 1997, 71: 7318-7327. PMID: 9311809, PMCID: PMC192076, DOI: 10.1128/jvi.71.10.7318-7327.1997.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBovine papillomavirus 1CattleCell LineCell MembraneErbB ReceptorsHumansInterleukin-3KineticsLeucineLysineMiceMolecular Sequence DataMutagenesis, Site-DirectedOncogene Proteins v-sisOncogene Proteins, ViralPoint MutationPolymerase Chain ReactionProtein Structure, SecondaryRatsReceptor, ErbB-2Receptor, Platelet-Derived Growth Factor betaReceptors, Platelet-Derived Growth FactorReceptors, VirusRecombinant Fusion ProteinsRetroviridae Proteins, OncogenicSequence AlignmentThreonineTransfectionConceptsBovine papillomavirus E5 proteinE5 proteinTransmembrane domainPDGF beta receptorAmino acidsCellular platelet-derived growth factor (PDGF) beta receptorReceptor mutantsJuxtamembrane domainPlatelet-derived growth factor beta receptorPutative transmembrane domainsMurine Ba/F3 cellsCarboxyl-terminal domainBa/F3 cellsV-sisReceptor tyrosine phosphorylationExtracellular juxtamembrane domainGrowth factor beta receptorSpecific amino acidsProductive interactionReceptor activationPlatelet-derived growth factor receptorAcidic amino acidsComplex formationThreonine residuesBeta receptors