%0 Journal Article
%T MAVS activates TBK1 and IKK¦Å through TRAFs in NEMO dependent and independent manner
%A Chenguang Wang
%A Ji-Ming Feng
%A Jianli Tao
%A Jianzhong Xi
%A Qifei Jiang
%A Run Fang
%A Xiang Zhou
%A Yukun Guan
%A Zhengfan Jiang
%J -
%D 2017
%R 10.1371/journal.ppat.1006720
%X Mitochondrial antiviral-signaling protein (MAVS) transmits signals from RIG-I-like receptors after RNA virus infections. However, the mechanism by which MAVS activates downstream components, such as TBK1 and IKK¦Á/¦Â, is unclear, although previous work suggests the involvement of NEMO or TBK1-binding proteins TANK, NAP1, and SINTBAD. Here, we report that MAVS-mediated innate immune activation is dependent on TRAFs, partially on NEMO, but not on TBK1-binding proteins. MAVS recruited TBK1/IKK¦Å by TRAFs that were pre-associated with TBK1/IKK¦Å via direct interaction between the coiled-coil domain of TRAFs and the SDD domain of TBK1/IKK¦Å. TRAF2£¿/£¿3£¿/£¿5£¿/£¿6£¿/£¿ cells completely lost RNA virus responses. TRAFs¡¯ E3 ligase activity was required for NEMO activation by synthesizing ubiquitin chains that bound to NEMO for NF-¦ÊB and TBK1/IKK¦Å activation. NEMO-activated IKK¦Á/¦Â were important for TBK1/IKK¦Å activation through IKK¦Á/¦Â-mediated TBK1/IKK¦Å phosphorylation. Moreover, individual TRAFs differently mediated TBK1/IKK¦Å activation and thus fine-tuned antiviral immunity under physiological conditions
%K 293T cells
%K Phosphorylation
%K Immunoprecipitation
%K Transcription factors
%K Ligases
%K Precipitates
%K Enzyme-linked immunoassays
%K HeLa cells
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006720