This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wan, J. Articles by Wu, Z. Search for Related Content PubMed PubMed Citation Articles by Wan, J. Articles by Wu, Z.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2004, p. 192-199, Vol. 24, No. 1
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.1.192-199.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Department of Biochemistry, Hong Kong University of Science & Technology,¹ Clinical Immunology Unit,³ Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, People’s Republic of China,⁴ Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland,² Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas,⁵ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada,⁶ and Department of Host Defense, Osaka University, Osaka,⁷,⁷ Department of Molecular Biology, Nagoya University, Nagoya,⁸ Japan⁸

Received 25 June 2003/ Returned for modification 20 August 2003/ Accepted 8 October 2003

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-B 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- 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.

This article has been cited by other articles:

• Yu, Y., Ge, N., Xie, M., Sun, W., Burlingame, S., Pass, A. K., Nuchtern, J. G., Zhang, D., Fu, S., Schneider, M. D., Fan, J., Yang, J. (2008). Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop Is Required for Interleukin (IL)-1-mediated Optimal NF{kappa}B and AP-1 Activation as Well as IL-6 Gene Expression. J. Biol. Chem. 283: 24497-24505 [Abstract] [Full Text]  
• Dawson, C. W., Laverick, L., Morris, M. A., Tramoutanis, G., Young, L. S. (2008). Epstein-Barr Virus-Encoded LMP1 Regulates Epithelial Cell Motility and Invasion via the ERK-MAPK Pathway. J. Virol. 82: 3654-3664 [Abstract] [Full Text]  
• Muroi, E., Manabe, S., Ikezaki, M., Urata, Y., Sato, S., Kondo, T., Ito, Y., Ihara, Y. (2007). C-Mannosylated peptides derived from the thrombospondin type 1 repeat enhance lipopolysaccharide-induced signaling in macrophage-like RAW264.7 cells. Glycobiology 17: 1015-1028 [Abstract] [Full Text]  
• Suzuki, S., Singhirunnusorn, P., Mori, A., Yamaoka, S., Kitajima, I., Saiki, I., Sakurai, H. (2007). Constitutive Activation of TAK1 by HTLV-1 Tax-dependent Overexpression of TAB2 Induces Activation of JNK-ATF2 but Not IKK-NF-{kappa}B. J. Biol. Chem. 282: 25177-25181 [Abstract] [Full Text]  
• Charalambous, C. T., Hannigan, A., Tsimbouri, P., McPhee, G. M., Wilson, J. B. (2007). Latent membrane protein 1-induced EGFR signalling is negatively regulated by TGF{alpha} prior to neoplasia. Carcinogenesis 28: 1839-1848 [Abstract] [Full Text]  
• Huye, L. E., Ning, S., Kelliher, M., Pagano, J. S. (2007). Interferon Regulatory Factor 7 Is Activated by a Viral Oncoprotein through RIP-Dependent Ubiquitination. Mol. Cell. Biol. 27: 2910-2918 [Abstract] [Full Text]  
• Bogoyevitch, M. A., Kobe, B. (2006). Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases. Microbiol. Mol. Biol. Rev. 70: 1061-1095 [Abstract] [Full Text]  
• Zhang, D., Song, L., Li, J., Wu, K., Huang, C. (2006). Coordination of JNK1 and JNK2 Is Critical for GADD45{alpha} Induction and Its Mediated Cell Apoptosis in Arsenite Responses. J. Biol. Chem. 281: 34113-34123 [Abstract] [Full Text]  
• Soni, V., Yasui, T., Cahir-McFarland, E., Kieff, E. (2006). LMP1 Transmembrane Domain 1 and 2 (TM1-2) FWLY Mediates Intermolecular Interactions with TM3-6 To Activate NF-{kappa}B. J. Virol. 80: 10787-10793 [Abstract] [Full Text]  
• Kondo, S., Seo, S. Y., Yoshizaki, T., Wakisaka, N., Furukawa, M., Joab, I., Jang, K. L., Pagano, J. S. (2006). EBV Latent Membrane Protein 1 Up-regulates Hypoxia-Inducible Factor 1{alpha} through Siah1-Mediated Down-regulation of Prolyl Hydroxylases 1 and 3 in Nasopharyngeal Epithelial Cells.. Cancer Res. 66: 9870-9877 [Abstract] [Full Text]  
• Santos, C. R., Blanco, S., Sevilla, A., Lazo, P. A. (2006). Vaccinia Virus B1R Kinase Interacts with JIP1 and Modulates c-Jun-Dependent Signaling.. J. Virol. 80: 7667-7675 [Abstract] [Full Text]  
• Brinkmann, M. M., Schulz, T. F. (2006). Regulation of intracellular signalling by the terminal membrane proteins of members of the Gammaherpesvirinae.. J. Gen. Virol. 87: 1047-1074 [Abstract] [Full Text]  
• Uemura, N., Kajino, T., Sanjo, H., Sato, S., Akira, S., Matsumoto, K., Ninomiya-Tsuji, J. (2006). TAK1 Is a Component of the Epstein-Barr Virus LMP1 Complex and Is Essential for Activation of JNK but Not of NF-{kappa}B. J. Biol. Chem. 281: 7863-7872 [Abstract] [Full Text]  
• Hirata, Y., Ohmae, T., Shibata, W., Maeda, S., Ogura, K., Yoshida, H., Kawabe, T., Omata, M. (2006). MyD88 and TNF Receptor-Associated Factor 6 Are Critical Signal Transducers in Helicobacter pylori-Infected Human Epithelial Cells. J. Immunol. 176: 3796-3803 [Abstract] [Full Text]  
• Wu, L., Nakano, H., Wu, Z. (2006). The C-terminal Activating Region 2 of the Epstein-Barr Virus-encoded Latent Membrane Protein 1 Activates NF-{kappa}B through TRAF6 and TAK1. J. Biol. Chem. 281: 2162-2169 [Abstract] [Full Text]  
• Wan, J., Zhang, W., Wu, L., Bai, T., Zhang, M., Lo, K.-w., Chui, Y.-l., Cui, Y., Tao, Q., Yamamoto, M., Akira, S., Wu, Z. (2006). BS69, a Specific Adaptor in the Latent Membrane Protein 1-Mediated c-Jun N-Terminal Kinase Pathway. Mol. Cell. Biol. 26: 448-456 [Abstract] [Full Text]  
• Xie, P., Bishop, G. A. (2004). Roles of TNF Receptor-Associated Factor 3 in Signaling to B Lymphocytes by Carboxyl-Terminal Activating Regions 1 and 2 of the EBV-Encoded Oncoprotein Latent Membrane Protein 1. J. Immunol. 173: 5546-5555 [Abstract] [Full Text]