Abstracts (complete list) - Wissenschaft Online

Dieter Kube, Diana Pinkert, Nils Schoof, Frederike von Bonin, Jennifer Theiss, Fred
Schaper, Johannes Bode, Martina Vockerodt
The EBV oncoprotein Latent Membrane Protein 1 affects the
expression of suppressors of cytokine signaling (SOCS) in
transformed B lymphocytes
Constitutive activation of signal transducer and activator of transcription 1 and 3
(STAT1, STAT3) is a distinctive feature of Epstein-Barr virus (EBV) infected B cells
characterized by the latency program III. The expression of STAT1 and the activation of
STAT3 in these cells can be modulated by the latent membrane protein 1 (LMP1), a
protein with known oncogenic properties. The mechanism of activation and the
functional responses are still unclear. The expression of full length LMP1 is responsible
for an enhanced STAT1 protein expression in Burkitt lymphoma cells (BL). STAT3 is
tyrosine phosphorylated without changes in STAT3 protein levels. A specific pattern of
Janus kinases (Jak) is activated by EBV, in part by LMP1 mediated activation of
respective cytokines. In LMP1 expressing BL cells suppressor of cytokine signaling
(SOCS) 3 mRNA is expressed involving transcriptional and posttranscriptional
mechanisms. The SOCS3 mRNA half life is regulated by LMP1 mediated p38/SAPK2
activation. Jak3 is involved in SOCS3 expression in BL cells as shown by specific
inhibitors. LMP1 activates SOCS3 promoter elements. Overexpression of SOCS3
prevents to a defined extend the activation of STAT3 by cytokines. SOCS1 mRNA is
expressed in all analysed cells independent from EBV. Our results support the role of
LMP1 in modulating cytokine signaling (supported by DFG Ku 954/7-2 and the
Graduiertenkolleg 1034).