@article{RodriguesPopovKayeetal.2013,
  author    = {Rodrigues, L{\´e}nia and Popov, Nikita and Kaye, Kenneth M. and Simas, J. Pedro},
  title     = {Stabilization of Myc through Heterotypic Poly-Ubiquitination by mLANA Is Critical for \(\gamma\)-Herpesvirus Lymphoproliferation},
  series = {PLoS PATHOGENS},
  volume    = {9},
  journal   = {PLoS PATHOGENS},
  number    = {8},
  doi       = {10.1371/journal.ppat.1003554},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131227},
  pages     = {e1003554},
  year      = {2013},
  abstract  = {Host colonization by lymphotropic \(\gamma\)-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 \(\gamma\)-cherpesviruses is still largely unknown. In this study, Myc was shown to be essential for the lymphotropic \(\gamma\)-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 posttranslational regulatory pathway of Myc. The molecular mechanism involves Myc heterotypic poly- ubiquitination mediated via the viral E3 ubiquitin- ligase mLANA protein. \(EC_5S^{mLANA}\) modulates cellular control of Myc turnover by antagonizing \(SCF^{Fbw7}\) mediated proteasomal degradation of Myc, mimicking \(SCF^{\beta-TrCP}\). The findings here reported reveal that modulation of Myc is essential for \(\gamma\)-herpesvirus persistent infection, establishing a link between virus induced lymphoproliferation and disease.},
  language  = {en}
}