Stabilization of Myc through Heterotypic Poly-Ubiquitination by mLANA Is Critical for \(\gamma\)-Herpesvirus Lymphoproliferation
Please always quote using this 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.…
Author: | Lénia Rodrigues, Nikita Popov, Kenneth M. Kaye, J. Pedro Simas |
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URN: | urn:nbn:de:bvb:20-opus-131227 |
Document Type: | Journal article |
Faculties: | Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften |
Language: | English |
Parent Title (English): | PLoS PATHOGENS |
Year of Completion: | 2013 |
Volume: | 9 |
Issue: | 8 |
Pagenumber: | e1003554 |
Source: | PLoS Pathogens 9(8): e1003554. doi:10.1371/journal.ppat.1003554 |
DOI: | https://doi.org/10.1371/journal.ppat.1003554 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten |
Tag: | B lymphocytes; C-MYC; Epstein-Barr-virus; beta-TRCP; cells; germinal center; latency; murine gammaherpesvirus 68; nuclear antigen; protein |
Release Date: | 2016/05/18 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung |