The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the Tumor Necrosis Factor receptor family

Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.
Cell (Impact Factor: 32.24). 03/1995; 80(3):389-99.
Source: PubMed


The cytoplasmic C-terminus of Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1) is essential for B lymphocyte growth transformation and is now shown to interact with a novel human protein (LMP1-associated protein 1 [LAP1]). LAP1 is homologous to a murine protein, tumor necrosis factor receptor-associated factor 2 (TRAF2), implicated in growth signaling from the p80 TNFR. A second novel protein (EBI6), induced by EBV infection, is the human homolog of a second murine TNFR-associated protein (TRAF1). LMP1 expression causes LAP1 and EBI6 to localize to LMP1 clusters in lymphoblast plasma membranes, and LMP1 coimmunoprecipitates with these proteins. LAP1 binds to the p80 TNFR, CD40, and the lymphotoxin-beta receptor, while EBI6 associates with the p80 TNFR. The interaction of LMP1 with these TNFR family-associated proteins is further evidence for their role in signaling and links LMP1-mediated transformation to signal transduction from the TNFR family.

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    • "Moreover, LMP1 does not reach LCL mRNA or protein levels until $2 weeks postinfection (Price et al., 2012) (Fig. 6.4). LMP1 acts as a constitutively active homologue to the human CD40 membrane protein (Mosialos et al., 1995) and is essential to the transforming capability of EBV (Kaye et al., 1993). Both CD40 and LMP1 signal through the NFkB pathway in a similar fashion (Luftig et al., 2003; Luftig et al., 2004), and inhibition of the NFkB pathway in LCLs results in spontaneous apoptosis (Cahir-McFarland et al., 2000). "
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