The Viral Oncoprotein LMP1 Exploits TRADD for Signaling by Masking Its Apoptotic Activity

• DOI: 10.1371/journal.pbio.0060008
• Publication Date: 2008-01-03T23:00:23Z
• Authors: Frank Schneider; Julia Neugebauer; Janine Griese; Nicola Liefold; Helmut Kutz; Cinthia Briseño; Arnd Kieser
• Keywords: TRADD; Viral infection

The tumor necrosis factor (TNF)-receptor 1-associated death domain protein (TRADD) mediates induction of apoptosis as well activation NF-kappaB by cellular TNF-receptor 1 (TNFR1). TRADD is also recruited the latent membrane (LMP1) oncoprotein Epstein-Barr virus, but its role in LMP1 signaling has remained enigmatic. In human B lymphocytes, we have generated, to our knowledge, first genetic knockout investigate TRADD's signal transduction. Our data from TRADD-deficient cells demonstrate that a critical mediator required for recruit and activate I-kappaB kinase beta (IKKbeta). However, contrast TNFR1, LMP1-induced does not induce apoptosis. Searching molecular basis this observation, characterized 16 C-terminal amino acids an autonomous unique virus-derived TRADD-binding domain. Replacing TNFR1 LMP1's converts into nonapoptotic receptor activates through TRAF6-dependent pathway, like unlike wild-type TNFR1. Thus, interaction with encodes transforming phenotype viral masks pro-apoptotic function.