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规范所需的生发中心激酶tnik nf-κb ebv和物信号在b细胞的癌蛋白lmp1和cd40受体.pdf

The Germinal Center Kinase TNIK Is Required for Canonical NF-kB and JNK Signaling in B-Cells by the EBV Oncoprotein LMP1 and the CD40 Receptor 1. 1. 1 1 2 ¨ 1 Anna Shkoda , Jennifer A. Town , Janine Griese , Michael Romio , Hakan Sarioglu , Thomas Knofel , 1 1 Fabian Giehler , Arnd Kieser * ¨ ¨ 1 Research Unit Gene Vectors, Helmholtz Zentrum Munchen - German Research Center for Environmental Health, Munchen, Germany, 2 Research Unit Protein Science, ¨ ¨ Helmholtz Zentrum Munchen - German Research Center for Environmental Health, Munchen, Germany 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-kB 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, TAK