2023
Sequence-independent activity of a predicted long disordered segment of the human papillomavirus type 16 L2 capsid protein during virus entry
Oh C, Buckley P, Choi J, Hierro A, DiMaio D. Sequence-independent activity of a predicted long disordered segment of the human papillomavirus type 16 L2 capsid protein during virus entry. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2307721120. PMID: 37819982, PMCID: PMC10589650, DOI: 10.1073/pnas.2307721120.Peer-Reviewed Original ResearchConceptsAmino acid sequenceAcid sequenceProtein segmentsVirus traffickingUnrelated cellular proteinsSequence-independent mannerIntracellular virus traffickingActivity of proteinsAmino acid segmentComplex biological functionsVirus entryTandem arraysProtein functionTrafficking factorsCellular proteinsEndosome membraneBiological functionsHPV16 pseudovirus infectionCellular factorsDiverse sequencesL2 capsid proteinsNoncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry
Choi J, DiMaio D. Noncanonical Rab9a action supports retromer-mediated endosomal exit of human papillomavirus during virus entry. PLOS Pathogens 2023, 19: e1011648. PMID: 37703297, PMCID: PMC10519607, DOI: 10.1371/journal.ppat.1011648.Peer-Reviewed Original ResearchConceptsRetromer-mediated endosomeHPV entryGTP-bound formDominant negative Rab7Intracellular vesicular transportRetrograde transport pathwayVirus entryEndosomal exitRab GTPasesRab proteinsVesicle traffickingGolgi transportCellular proteinsVesicular transportProtein cargoKnockdown cellsIntracellular traffickingRab9AIncoming virusRab7EndosomesTraffickingTransport pathwaysProteinKey roleHPV is a cargo for the COPI sorting complex during virus entry
Harwood M, Woo T, Takeo Y, DiMaio D, Tsai B. HPV is a cargo for the COPI sorting complex during virus entry. Science Advances 2023, 9: eadc9830. PMID: 36662862, PMCID: PMC9858521, DOI: 10.1126/sciadv.adc9830.Peer-Reviewed Original ResearchConceptsCoat protein complex ITrans-Golgi networkProtein complex IGene knockdown strategyVirus entryCOPI complexProtein complexesCellular fractionationUnbiased proteomicsRetrograde traffickingCytoplasmic segmentGolgi stacksCellular cargoL2 mutantKnockdown strategyGolgi apparatusComplex IIncoming virusCell surfaceGolgiHost factorsCargoComplexesMutantsEndosomes
2022
Human Papillomavirus L2 Capsid Protein Stabilizes γ-Secretase during Viral Infection
Crite M, DiMaio D. Human Papillomavirus L2 Capsid Protein Stabilizes γ-Secretase during Viral Infection. Viruses 2022, 14: 804. PMID: 35458534, PMCID: PMC9027364, DOI: 10.3390/v14040804.Peer-Reviewed Original ResearchConceptsTM domainΓ-secretaseVirus traffickingCellular transmembrane proteinsNon-canonical rolePutative TM domainRetrograde transport pathwayΓ-secretase complexSubstrate proteinsMinor capsid protein L2Transmembrane proteinCatalytic subunitMutational studiesEndosomal membranesIntracellular traffickingProtein L2Cellular proteasesCellular factorsL2 capsid proteinsTM mutantsCapsid proteinHPV entryTraffickingL2 proteinProtein
2020
TBC1D5-Catalyzed Cycling of Rab7 Is Required for Retromer-Mediated Human Papillomavirus Trafficking during Virus Entry
Xie J, Heim EN, Crite M, DiMaio D. TBC1D5-Catalyzed Cycling of Rab7 Is Required for Retromer-Mediated Human Papillomavirus Trafficking during Virus Entry. Cell Reports 2020, 31: 107750. PMID: 32521275, PMCID: PMC7339955, DOI: 10.1016/j.celrep.2020.107750.Peer-Reviewed Original ResearchConceptsGTPase-activating proteinsRetrograde transport pathwayVirus entryRetromer activityHPV traffickingTrafficking complexMembrane recruitmentRetromer complexRab7-GTPCellular proteinsCellular compartmentsEndosome membraneRetromerRetrograde pathwayArtificial proteinsL2 capsid proteinsCapsid proteinRab7HPV entryTraffickingTBC1D5ProteinGTPTransport pathwaysPathwayCell-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
2018
Cell-Penetrating Peptide Mediates Intracellular Membrane Passage of Human Papillomavirus L2 Protein to Trigger Retrograde Trafficking
Zhang P, da Silva G, Deatherage C, Burd C, DiMaio D. Cell-Penetrating Peptide Mediates Intracellular Membrane Passage of Human Papillomavirus L2 Protein to Trigger Retrograde Trafficking. Cell 2018, 174: 1465-1476.e13. PMID: 30122350, PMCID: PMC6128760, DOI: 10.1016/j.cell.2018.07.031.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCapsid ProteinsCell-Penetrating PeptidesEndosomesGolgi ApparatusGreen Fluorescent ProteinsHEK293 CellsHeLa CellsHuman papillomavirus 16HumansMutagenesisOncogene Proteins, ViralProtein TransportRecombinant Fusion ProteinsSequence AlignmentVirus AttachmentVirus InternalizationConceptsCell-penetrating peptidesTrans-Golgi networkNormal cell physiologyL2 proteinRetrograde transport pathwayShort protein segmentsHPV L2 proteinTrafficking factorsRetrograde traffickingCationic cell-penetrating peptidesCell physiologyEndosomal membranesProtein segmentsC-terminusBiological roleNon-enveloped virusesRetrograde pathwayL2 capsid proteinsMembrane passageCell penetrating peptideCapsid proteinViral proteinsProteinRetromerTransport pathwaysγ-Secretase promotes membrane insertion of the human papillomavirus L2 capsid protein during virus infection
Inoue T, Zhang P, Zhang W, Goodner-Bingham K, Dupzyk A, DiMaio D, Tsai B. γ-Secretase promotes membrane insertion of the human papillomavirus L2 capsid protein during virus infection. Journal Of Cell Biology 2018, 217: 3545-3559. PMID: 30006461, PMCID: PMC6168257, DOI: 10.1083/jcb.201804171.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
2015
Direct Binding of Retromer to Human Papillomavirus Type 16 Minor Capsid Protein L2 Mediates Endosome Exit during Viral Infection
Popa A, Zhang W, Harrison MS, Goodner K, Kazakov T, Goodwin EC, Lipovsky A, Burd CG, DiMaio D. Direct Binding of Retromer to Human Papillomavirus Type 16 Minor Capsid Protein L2 Mediates Endosome Exit during Viral Infection. PLOS Pathogens 2015, 11: e1004699. PMID: 25693203, PMCID: PMC4334968, DOI: 10.1371/journal.ppat.1004699.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkRetromer cargoTransmembrane proteinGolgi apparatusDirect bindingCoat protein complexCellular transmembrane proteinsVirus entryMinor capsid proteinCarboxy-terminal segmentProtein complexesL2 minor capsid proteinMinor capsid protein L2Early endosomesVesicular transportRetromerPlasma membraneEndosomal membranesBinding motifProtein L2Capsid proteinEndosomesL2 proteinViral componentsProtein
2013
Genome-wide siRNA screen identifies the retromer as a cellular entry factor for human papillomavirus
Lipovsky A, Popa A, Pimienta G, Wyler M, Bhan A, Kuruvilla L, Guie MA, Poffenberger AC, Nelson CD, Atwood WJ, DiMaio D. Genome-wide siRNA screen identifies the retromer as a cellular entry factor for human papillomavirus. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 7452-7457. PMID: 23569269, PMCID: PMC3645514, DOI: 10.1073/pnas.1302164110.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkHPV entryGenome-wide screenRetromer subunitsCellular genesScreen identifiesRetromerLate endosomesPotential antiviral targetsMultiple subunitsRetrograde pathwayTransport factorsCapsid proteinHeLa cellsCell entryAntiviral targetEndosomesGolgiVirus entryStable complexesEfficient infectionSubunitsHPV proteinsProteinImportant insights
2001
Induced senescence in HeLa cervical carcinoma cells containing elevated telomerase activity and extended telomeres.
Goodwin E, DiMaio D. Induced senescence in HeLa cervical carcinoma cells containing elevated telomerase activity and extended telomeres. Molecular Cancer Research 2001, 12: 525-34. PMID: 11714633.Peer-Reviewed Original ResearchConceptsTumor suppressor pathwayHeLa cervical carcinoma cellsExtended telomeresReplicative senescenceHTERT geneSuppressor pathwayTelomerase activityGrowth arrestCervical carcinoma cellsRepression of telomeraseElevated telomerase activitySomatic human cellsNormal somatic human cellsShort telomeresGrowth-arrested stateSenescence-associated beta-galactosidase expressionHPV E6/E7 expressionGrowth-arrested cellsHeLa cell clonesProfound growth arrestRole of telomeraseE6/E7 genesBeta-galactosidase expressionErosion of telomeresCarcinoma cells
2000
Repression 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 oncogenesE2F-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 complexesRapid 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 ProteinsCattleCdc25 PhosphatasesCDC2-CDC28 KinasesCell 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 levels
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 substitutionsTransactivation-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: 3925-34. 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 gene