ArticlePLoS biology2012
The germinal center kinase TNIK is required for canonical NF-κB and JNK signaling in B-cells by the EBV oncoprotein LMP1 and the CD40 receptor.
Article in PLoS biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 79 citations in OpenAlex.
- A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models.Nature biotechnology · 2025Trial
- CK2 in triple-negative breast cancer: oncogenic signaling networks and emerging CK2 inhibitor-based combination therapies.Clinical and experimental medicine · 2026Review
- CRISPR Screens Reveal Epstein-Barr Virus-activated JunB as a Key Lymphoblastoid B cell Dependency Factor that Represses Cyclin Dependent Kinase Inhibitor P18INK4c.bioRxiv : the preprint server for biology · 2026Article
- Epstein-Barr Virus Latent Membrane Protein 1 Suppresses Ferroptosis via Pentose Phosphate Pathway and Glutathione Metabolism.bioRxiv : the preprint server for biology · 2026Article
- Toward Combinatorial Strategies to Improve Proximal Tubule Recovery Following Acute Kidney Injury.Seminars in nephrology · 2026Review
- Epstein-Barr virus latent membrane protein 1 subverts IMPDH pathways to drive B-cell oncometabolism.PLoS pathogens · 2025Article
- TNIK-driven regulation of ERK5 transcriptional activity in endothelial cells.Frontiers in cardiovascular medicine · 2025Article
- TNIK in disease: from molecular insights to therapeutic prospects.Apoptosis : an international journal on programmed cell death · 2024Review
- Article
- Kinome and phosphoproteome reprogramming underlies the aberrant immune responses in critically ill COVID-19 patients.Clinical proteomics · 2024Article
- Epstein-Barr virus-driven B cell lymphoma mediated by a direct LMP1-TRAF6 complex.Nature communications · 2024Article
- Transcriptome analysis to explore the mechanism of downregulated TNIK influencing the effect of risperidone.Frontiers in pharmacology · 2024Article
- TNIK is a conserved regulator of glucose and lipid metabolism in obesity.Science advances · 2023Article
- Article
- Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis.Frontiers in cardiovascular medicine · 2023Article
- TNIK regulation of interferon signaling and endothelial cell response to virus infection.Frontiers in cardiovascular medicine · 2023Article
- Promotion of nonalcoholic steatohepatitis by RNA NLife metabolism · 2022Article
- TNIK Inhibition Has Dual Synergistic Effects on Tumor and Associated Immune Cells.Advanced biology · 2022Article
- Quantification of adaptive forces on SNP rs1010211 due to viral zoonotic pathogens.Journal of biological physics · 2022Article
- Longitudinal Single-Cell Dynamics of Chromatin Accessibility and Mitochondrial Mutations in Chronic Lymphocytic Leukemia Mirror Disease History.Cancer discovery · 2021Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor necrosis factor-receptor-associated factor 2 (TRAF2)- and Nck-interacting kinase (TNIK) is a ubiquitously expressed member of the germinal center kinase family. The TNIK functions in hematopoietic cells and the role of TNIK-TRAF interaction remain largely unknown. By functional proteomics we identified TNIK as interaction partner of the latent membrane protein 1 (LMP1) signalosome in primary human B-cells infected with the Epstein-Barr tumor virus (EBV). RNAi-mediated knockdown proved a critical role for TNIK in canonical NF-κB and c-Jun N-terminal kinase (JNK) activation by the major EBV oncoprotein LMP1 and its cellular counterpart, the B-cell co-stimulatory receptor CD40. Accordingly, TNIK is mandatory for proliferation and survival of EBV-transformed B-cells. TNIK forms an activation-induced complex with the critical signaling mediators TRAF6, TAK1/TAB2, and IKKβ, and mediates signalosome formation at LMP1. TNIK directly binds TRAF6, which bridges TNIK's interaction with the C-terminus of LMP1. Separate TNIK domains are involved in NF-κB and JNK signaling, the N-terminal TNIK kinase domain being essential for IKKβ/NF-κB and the C-terminus for JNK activation. We therefore suggest that TNIK orchestrates the bifurcation of both pathways at the level of the TRAF6-TAK1/TAB2-IKK complex. Our data establish TNIK as a novel key player in TRAF6-dependent JNK and NF-κB signaling and a transducer of activating and transforming signals in human B-cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.