dc.contributor.author | Rodrigues, Lénia | en_US |
dc.contributor.author | Popov, Nikita | en_US |
dc.contributor.author | Kaye, Kenneth M. | en_US |
dc.contributor.author | Simas, J. Pedro | en_US |
dc.date.accessioned | 2014-03-01T02:24:50Z | |
dc.date.issued | 2013 | en_US |
dc.identifier.citation | Rodrigues, 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.issn | 1553-7366 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:11855819 | |
dc.description.abstract | Host 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.iso | en_US | en |
dc.publisher | Public Library of Science | en |
dc.relation.isversionof | doi:10.1371/journal.ppat.1003554 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738482/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | Biology | en |
dc.subject | Biochemistry | en |
dc.subject | Proteins | en |
dc.subject | Immune System Proteins | en |
dc.subject | Protein Interactions | en |
dc.subject | Microbiology | en |
dc.subject | Immunity | en |
dc.subject | Humoral Immunity | en |
dc.subject | Immunoregulation | en |
dc.subject | Virology | en |
dc.subject | Viral Replication | en |
dc.subject | Viral Latency | en |
dc.subject | Animal Models of Infection | en |
dc.subject | Viral Enzymes | en |
dc.subject | Viral Persistence and Latency | en |
dc.subject | Virulence Factors and Mechanisms | en |
dc.subject | Viruses and Cancer | en |
dc.subject | Host-Pathogen Interaction | en |
dc.subject | Pathogenesis | en |
dc.subject | Molecular Cell Biology | en |
dc.subject | Cell Division | en |
dc.subject | Cyclins | en |
dc.subject | Signal Transduction | en |
dc.subject | Signaling in Selected Disciplines | en |
dc.subject | Oncogenic Signaling | en |
dc.title | Stabilization of Myc through Heterotypic Poly-Ubiquitination by mLANA Is Critical for γ-Herpesvirus Lymphoproliferation | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | PLoS Pathogens | en |
dash.depositing.author | Kaye, Kenneth M. | en_US |
dc.date.available | 2014-03-01T02:24:50Z | |
dc.identifier.doi | 10.1371/journal.ppat.1003554 | * |
dash.contributor.affiliated | Kaye, Kenneth | |