The NPC derived C15 LMP1 protein confers enhanced activation of NF-κB and induction of the EGFR in epithelial cells (original) (raw)

Oncogene volume 16, pages 1869–1877 (1998)Cite this article

Abstract

The Epstein–Barr Virus (EBV) LMP1 protein is frequently expressed in nasopharyngeal carcinoma and is essential for the transforming effects of EBV. Analysis of LMP1 genes isolated from tumor biopsies has revealed considerable sequence variation including deletion of amino acids 343–352. Several studies have suggested that this sequence variation could enhance the transforming potential of LMP1. LMP1 has profound effects on cellular gene expression mediated in part through activation of the NF-κB transcription factor. In addition, LMP1 engages the TRAF 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 NF-κB and also to induce expression of the EGFR. The data suggest that the C15-LMP1 protein activates NF-κB more efficiently and induces higher levels of the EGFR. Analysis of chimeric LMP1 proteins indicates that the amino terminal 181 amino acids of C15-LMP1 confer this increased signaling capability, and that deletion of amino acids 343–352 does not affect these properties. Finally, these data provide evidence that five amino acid changes within the transmembrane domain in the C15-LMP1 protein lead to enhanced NF-κB activation and EGFR induction.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, 27599, North Carolina, USA
    William E Miller & Nancy Raab-Traub
  2. Department of Biology and Curriculum in Genetics, University of North Carolina School of Medicine, Chapel Hill, 27599, North Carolina, USA
    Albert S Baldwin Jr
  3. Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, 27599, North Carolina, USA
    William E Miller, Jeanette L Cheshire, Albert S Baldwin Jr & Nancy Raab-Traub

Authors

  1. William E Miller
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  2. Jeanette L Cheshire
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  3. Albert S Baldwin Jr
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  4. Nancy Raab-Traub
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Miller, W., Cheshire, J., Baldwin, A. et al. The NPC derived C15 LMP1 protein confers enhanced activation of NF-κB and induction of the EGFR in epithelial cells.Oncogene 16, 1869–1877 (1998). https://doi.org/10.1038/sj.onc.1201696

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