THE NPC DERIVED C15 LMP1 PROTEIN CONFERS ENHANCED ACTIVATION OF NF-KAPPA-B AND INDUCTION OF THE EGFR IN EPITHELIAL-CELLS

The Epstein-Barr Virus (EBV) LMP1 protein is frequently expressed in n asopharyngeal carcinoma and is essential for the transforming effects of EBV. Analysis of LMP1 genes isolated from tumor biopsies has reveal ed considerable sequence variation including deletion of amino acids 3 43-352. Several studies have suggested that this sequence variation co uld enhance the transforming potential of LMP1. LMP1 has profound effe cts on cellular gene expression mediated in part through activation of the NF-kappa B transcription factor. In addition, LMP1 engages the TR AF signaling pathway resulting in the induction of EGFR expression, In this study, the LMP1 proteins derived from the laboratory strain B95- 8 and the NPC strain C15 were analysed for their ability to activate N F-kappa B and also to induce expression of the EGFR. The data suggest that the C15-LMP1 protein activates NF-kappa B more efficiently and in duces higher levels of the EGFR. Analysis of chimeric LMP1 proteins in dicates that the amino terminal 181 amino acids of C15-LMP1 confer thi s increased signaling capability, and that deletion of amino acids 343 -352 does not affect these properties. Finally, these data provide evi dence that five amino acid changes within the transmembrane domain in the C15-LMP1 protein lead to enhanced NF-kappa B activation and EGFR i nduction.