ArticleJournal of virology2002
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.
Article in Journal of virology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 60 citations in OpenAlex.
- A CRISPR-Cas9 screen Reveals STEEP1 as a Key Host Dependency Factor for Epstein-Barr Virus Latent Membrane Protein 1 Trafficking and Signaling.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic Regulation of MAP3K8 in EBV-Associated Gastric Carcinoma.International journal of molecular sciences · 2023Article
- Review
- A central role of IKK2 and TPL2 in JNK activation and viral B-cell transformation.Nature communications · 2020Article
- Tumor progression locus 2 (TPL2) in tumor-promoting Inflammation, Tumorigenesis and Tumor Immunity.Theranostics · 2020Review
- Inhibition of HGF/MET signaling decreases overall tumor burden and blocks malignant conversion in Tpl2-related skin cancer.Oncogenesis · 2019Article
- NF-κB Pathways in the Pathogenesis of Multiple Sclerosis and the Therapeutic Implications.Frontiers in molecular neuroscience · 2016Review
- Article
- Tumor progression locus 2 (Tpl2) kinase as a novel therapeutic target for cancer: double-sided effects of Tpl2 on cancer.International journal of molecular sciences · 2015Review
- TPL2 kinase is a suppressor of lung carcinogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- [Effects of tea polyphenols on the expression of NF-κB, COX-2 and survivin in Lewis lung carcinoma xenografts in C57BL/6 mice].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2012Article
- Genome-wide siRNA screen for mediators of NF-κB activation.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Cot/tpl2 (MAP3K8) mediates myeloperoxidase activity and hypernociception following peripheral inflammation.The Journal of biological chemistry · 2010Article
- Epstein-Barr virus-encoded LMP1 regulates epithelial cell motility and invasion via the ERK-MAPK pathway.Journal of virology · 2008Article
- Epigenetic regulation of microRNA-370 by interleukin-6 in malignant human cholangiocytes.Oncogene · 2008Article
- PRA1 promotes the intracellular trafficking and NF-kappaB signaling of EBV latent membrane protein 1.The EMBO journal · 2006Article
- Expression of the Tpl2/Cot oncogene in human T-cell neoplasias.Molecular cancer · 2004Article
- Mutational activation of the MAP3K8 protooncogene in lung cancer.Genes, chromosomes & cancer · 2004Article
- Article
- The COOH-terminal domain of wild-type Cot regulates its stability and kinase specific activity.Molecular and cellular biology · 2003Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
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 activation, which largely depends on TRAF2. The ability of Tpl-2 to influence LMP1-induced NF-kappaB occurs through modulation of both IkappaBalpha and p105 functions. Furthermore, Tpl-2 was found to influence the expression of angiogenic mediators, such as COX-2 in LMP1-transfected cells. These data identify Tpl-2 as a component of LMP1 signaling downstream of TRAF2 and as a modulator of LMP1-mediated effects.
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