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dc.contributor.authorRodrigues, Léniaen_US
dc.contributor.authorPopov, Nikitaen_US
dc.contributor.authorKaye, Kenneth M.en_US
dc.contributor.authorSimas, J. Pedroen_US
dc.date.accessioned2014-03-01T02:24:50Z
dc.date.issued2013en_US
dc.identifier.citationRodrigues, Lénia, Nikita Popov, Kenneth M. Kaye, and J. Pedro Simas. 2013. “Stabilization of Myc through Heterotypic Poly-Ubiquitination by mLANA Is Critical for γ-Herpesvirus Lymphoproliferation.” PLoS Pathogens 9 (8): e1003554. doi:10.1371/journal.ppat.1003554. http://dx.doi.org/10.1371/journal.ppat.1003554.en
dc.identifier.issn1553-7366en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11855819
dc.description.abstractHost colonization by lymphotropic γ-herpesviruses depends critically on expansion of viral genomes in germinal center (GC) B-cells. Myc is essential for the formation and maintenance of GCs. Yet, the role of Myc in the pathogenesis of γ-herpesviruses is still largely unknown. In this study, Myc was shown to be essential for the lymphotropic γ-herpesvirus MuHV-4 biology as infected cells exhibited increased expression of Myc signature genes and the virus was unable to expand in Myc defficient GC B-cells. We describe a novel strategy of a viral protein activating Myc through increased protein stability resulting in increased progression through the cell cycle. This is acomplished by modulating a physiological post-translational regulatory pathway of Myc. The molecular mechanism involves Myc heterotypic poly-ubiquitination mediated via the viral E3 ubiquitin-ligase mLANA protein. EC5SmLANA modulates cellular control of Myc turnover by antagonizing SCFFbw7 mediated proteasomal degradation of Myc, mimicking SCFβ-TrCP. The findings here reported reveal that modulation of Myc is essential for γ-herpesvirus persistent infection, establishing a link between virus induced lymphoproliferation and disease.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.ppat.1003554en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738482/pdf/en
dash.licenseLAAen_US
dc.subjectBiologyen
dc.subjectBiochemistryen
dc.subjectProteinsen
dc.subjectImmune System Proteinsen
dc.subjectProtein Interactionsen
dc.subjectMicrobiologyen
dc.subjectImmunityen
dc.subjectHumoral Immunityen
dc.subjectImmunoregulationen
dc.subjectVirologyen
dc.subjectViral Replicationen
dc.subjectViral Latencyen
dc.subjectAnimal Models of Infectionen
dc.subjectViral Enzymesen
dc.subjectViral Persistence and Latencyen
dc.subjectVirulence Factors and Mechanismsen
dc.subjectViruses and Canceren
dc.subjectHost-Pathogen Interactionen
dc.subjectPathogenesisen
dc.subjectMolecular Cell Biologyen
dc.subjectCell Divisionen
dc.subjectCyclinsen
dc.subjectSignal Transductionen
dc.subjectSignaling in Selected Disciplinesen
dc.subjectOncogenic Signalingen
dc.titleStabilization of Myc through Heterotypic Poly-Ubiquitination by mLANA Is Critical for γ-Herpesvirus Lymphoproliferationen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Pathogensen
dash.depositing.authorKaye, Kenneth M.en_US
dc.date.available2014-03-01T02:24:50Z
dc.identifier.doi10.1371/journal.ppat.1003554*
dash.contributor.affiliatedKaye, Kenneth


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