The oncogenic protein kinase Tpl-2/Cot contributes to Epstein-Barr virus-encoded latent infection membrane protein 1-induced NF-kappaB signaling downstream of TRAF2

Journal of Virology
Aristides G EliopoulosLawrence S Young

Abstract

The Epstein-Barr virus-encoded latent infection membrane protein 1 (LMP1) is a pleiotropic protein, the activities of which include effects on cell transformation and phenotype, growth, and survival. The ability of LMP1 to mediate at least some of these phenomena could be attributed to the activation of the transcription factor NF-kappaB. LMP1 promotes NF-kappaB activation through the recruitment of the adapter protein TRAF2 and the formation of a dynamic multiprotein complex that includes the NF-kappaB kinase, the IkappaB kinases, and their downstream targets, IkappaBs and p105. In this study, we have identified the oncogenic kinase Tpl-2/Cot as a novel component of LMP1-induced NF-kappaB signaling. We show that Tpl-2 is expressed in primary biopsies from patients with nasopharyngeal carcinoma and Hodgkin's disease, where LMP1 is also found. Inducible expression of LMP1 promotes the activation of Tpl-2, and a catalytically inactive Tpl-2 mutant suppresses LMP1-induced NF-kappaB signaling. In colocalization and coimmunoprecipitation experiments, Tpl-2 and TRAF2 were found to interact with Tpl-2 functioning downstream of TRAF2. Consistent with this observation, catalytically inactive Tpl-2 also blocked CD40-mediated NF-kappaB ac...Continue Reading

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Citations

May 31, 2003·International Journal of Hematology·Im-Soon LeeSeong Hoe Park
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Benjamin E GewurzElliott Kieff
Mar 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Katerina GkirtzimanakiAristides G Eliopoulos
Aug 26, 2010·The Journal of Biological Chemistry·Irene Soria-CastroSusana Alemany
Sep 18, 2002·The EMBO Journal·Aristides G EliopoulosPhilip N Tsichlis
Jan 18, 2008·Journal of Virology·Christopher W DawsonLawrence S Young
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