Stabilization of Myc through Heterotypic Poly-Ubiquitination by mLANA Is Critical for \(\gamma\)-Herpesvirus Lymphoproliferation
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-131227
- 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 describeHost 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.…
Autor(en): | Lénia Rodrigues, Nikita Popov, Kenneth M. Kaye, J. Pedro Simas |
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URN: | urn:nbn:de:bvb:20-opus-131227 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | PLoS PATHOGENS |
Erscheinungsjahr: | 2013 |
Band / Jahrgang: | 9 |
Heft / Ausgabe: | 8 |
Seitenangabe: | e1003554 |
Originalveröffentlichung / Quelle: | PLoS Pathogens 9(8): e1003554. doi:10.1371/journal.ppat.1003554 |
DOI: | https://doi.org/10.1371/journal.ppat.1003554 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten |
Freie Schlagwort(e): | B lymphocytes; C-MYC; Epstein-Barr-virus; beta-TRCP; cells; germinal center; latency; murine gammaherpesvirus 68; nuclear antigen; protein |
Datum der Freischaltung: | 18.05.2016 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung |