TY  - JOUR
A1  - Rodrigues, Lénia
A1  - Popov, Nikita
A1  - Kaye, Kenneth M.
A1  - Simas, J. Pedro
T1  - Stabilization of Myc through Heterotypic Poly-Ubiquitination by mLANA Is Critical for \(\gamma\)-Herpesvirus Lymphoproliferation
JF  - PLoS PATHOGENS
N2  - 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.
KW  - latency
KW  - murine gammaherpesvirus 68
KW  - Epstein-Barr-virus
KW  - C-MYC
KW  - nuclear antigen
KW  - germinal center
KW  - B lymphocytes
KW  - protein
KW  - cells
KW  - beta-TRCP
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131227
VL  - 9
IS  - 8
ER  - 
TY  - JOUR
A1  - Tony, H. P.
A1  - Lehrnbecher, T.
A1  - Merz, H.
A1  - Sebald, Werner
A1  - Wilhelm, M.
T1  - Regulation of IL-4 responsiveness in lymphoma B cells
N2  - The responsiveness to IL-4 with and without costimulation with anti-IgM antibodies or phorbolester was studied in 35 cases of low grade non-Hodgkin Iymphoma by analyzing enhancement of CD23 and HLA dass li expression. The predominant phenotype responds directly to IL-4. Separate differentiation states can be distinguished according to coordinate or differential upregulation of CD23 and HLA dass II molecules by IL-4 alone, and differences in responsiveness to anti-IgM antibodies. A particular subgroup of B-lymphoma cells defines a separate stage of B-eeil differentiation. They fail to express high affinity binding sites for IL-4 and accordingly do not respond to IL-4- mediated signals. Cross-linking membrane lgM receptors or direct activation of protein kinase C via phorbolester induces IL-4 receptor expression and subsequent IL-4 reactivity.
KW  - Biochemie
KW  - B lymphocytes
KW  - CD23
KW  - CLL
KW  - HLA class ll
KW  - IL-4
KW  - IL-4-receptor
KW  - membrane immunoglobulin
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62520
ER  -