Elucidation of the c-Jun N-Terminal Kinase Pathway Mediated by Epstein-Barr Virus-Encoded Latent Membrane Protein 1

Jun Wan, Luguo Sun, Jennifer Woo Mendoza, Yiu Loon Chui, Dolly P. Huang, Zhijian J. Chen, Nobutaka Suzuki, Shinobu Suzuki, Wen Chen Yeh, Shizuo Akira, Kunihiro Matsumoto, Zheng Gang Liu, Zhenguo Wu

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Epstein-Barr virus (EBV) is associated with several human diseases including infectious mononucleosis and nasopharyngeal carcinoma. EBV-encoded latent membrane protein 1 (LMP1) is oncogenic and indispensable for cellular transformation caused by EBV. Expression of LMP1 in host cells constitutively activates both the c-Jun N-terminal kinase (JNK) and NF-KB pathways, which contributes to the oncogenic effect of LMP1. However, the underlying signaling mechanisms are not very well understood. Based mainly on overexpression studies with various dominant-negative constructs, LMP1 was generally thought to functionally mimic members of the tumor necrosis factor (TNF) receptor superfamily in signaling. In contrast to the prevailing paradigm, using embryonic fibroblasts from different knockout mice and the small interfering RNA technique, we find that the LMP1-mediated JNK pathway is distinct from those mediated by either TNF-α or interleukin-1. Moreover, we have further elucidated the LMP1-mediated JNK pathway by demonstrating that LMP1 selectively utilizes TNF receptor-associated factor 6, TAK1/TAB1, and c-Jun N-terminal kinase kinases 1 and 2 to activate JNK.

Original languageEnglish (US)
Pages (from-to)192-199
Number of pages8
JournalMolecular and cellular biology
Volume24
Issue number1
DOIs
StatePublished - Jan 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Wan, J., Sun, L., Mendoza, J. W., Chui, Y. L., Huang, D. P., Chen, Z. J., Suzuki, N., Suzuki, S., Yeh, W. C., Akira, S., Matsumoto, K., Liu, Z. G., & Wu, Z. (2004). Elucidation of the c-Jun N-Terminal Kinase Pathway Mediated by Epstein-Barr Virus-Encoded Latent Membrane Protein 1. Molecular and cellular biology, 24(1), 192-199. https://doi.org/10.1128/MCB.24.1.192-199.2004