PuSH - Publication Server of Helmholtz Zentrum München

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.

PLoS Biol. 10:e1001376 (2012)
Publ. Version/Full Text Volltext DOI
Open Access Gold
Creative Commons Lizenzvertrag
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.
Altmetric
Additional Metrics?
Tags
PROT-CF
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Keywords EPSTEIN-BARR-VIRUS; LATENT MEMBRANE-PROTEIN; NCK-INTERACTING KINASE; WNT TARGET GENES; GROWTH TRANSFORMATION; MEDIATES ACTIVATION; BINDING-SITE; MEMBRANE-PROTEIN-1; PATHWAY; TRAF6
ISSN (print) / ISBN 1544-9173
e-ISSN 1545-7885
Journal PLoS Biology
Quellenangaben Volume: 10, Issue: 8, Pages: , Article Number: e1001376 Supplement: ,
Publisher Public Library of Science (PLoS)
Reviewing status Peer reviewed