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 proteins
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
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 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 levels
1998
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
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 gene
1996
Activation of the endogenous p53 growth inhibitory pathway in HeLa cervical carcinoma cells by expression of the bovine papillomavirus E2 gene.
Hwang E, Naeger L, DiMaio D. Activation of the endogenous p53 growth inhibitory pathway in HeLa cervical carcinoma cells by expression of the bovine papillomavirus E2 gene. Oncogene 1996, 12: 795-803. PMID: 8632901.Peer-Reviewed Original ResearchMeSH KeywordsBovine papillomavirus 1CDC2-CDC28 KinasesCell DivisionCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclinsDNA ReplicationDNA-Binding ProteinsEnzyme InhibitorsFemaleGene Expression Regulation, NeoplasticGene Expression Regulation, ViralGenes, ViralHeLa CellsHumansModels, BiologicalPhosphorylationProtein Serine-Threonine KinasesTumor Suppressor Protein p53Uterine Cervical NeoplasmsViral ProteinsConceptsTumor suppressor proteinGrowth inhibitory pathwaySuppressor proteinHeLa cellsP21/waf1Kinase activityE2 geneBPV E2 proteinP53 tumor suppressor proteinCdk2/cyclin E kinase activityCyclin-dependent kinase inhibitorGrowth regulatory pathwaysHeLa cervical carcinoma cellsP53-responsive genesCell cycle regulatory proteinsCDK kinase activityCyclin E kinase activityCycle regulatory proteinsDependent kinase inhibitorG1 cell cycle regulatory proteinsB-MybTranscription factorsRegulatory proteinsRegulatory pathwaysP105Rb
1993
Inhibition of cervical carcinoma cell line proliferation by the introduction of a bovine papillomavirus regulatory gene
Hwang E, Riese D, Settleman J, Nilson L, Honig J, Flynn S, DiMaio D. Inhibition of cervical carcinoma cell line proliferation by the introduction of a bovine papillomavirus regulatory gene. Journal Of Virology 1993, 67: 3720-3729. PMID: 8389903, PMCID: PMC237735, DOI: 10.1128/jvi.67.7.3720-3729.1993.Peer-Reviewed Original ResearchConceptsBPV E2 proteinGene expressionCervical carcinoma cell linesRegulatory genesHPV gene expressionCarcinoma cell linesCell linesE2 proteinHeLa cellsConsequence of abrogationP53 tumor suppressor proteinHPV18 E6Tumor suppressor proteinE2 geneDestabilization of p53HT-3 cellsGrowth inhibitionBPV E2Simian virus 40Suppressor proteinEpithelial cell lineHuman papillomavirus E6Cell cycleGenesS phase