文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

线粒体抗病毒信号蛋白通过肿瘤坏死因子受体相关因子以依赖和不依赖核因子κB必需调节蛋白的方式激活TANK结合激酶1和IKKε。

MAVS activates TBK1 and IKKε through TRAFs in NEMO dependent and independent manner.

作者信息

Fang Run, Jiang Qifei, Zhou Xiang, Wang Chenguang, Guan Yukun, Tao Jianli, Xi Jianzhong, Feng Ji-Ming, Jiang Zhengfan

机构信息

Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China.

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

出版信息

PLoS Pathog. 2017 Nov 10;13(11):e1006720. doi: 10.1371/journal.ppat.1006720. eCollection 2017 Nov.

DOI:10.1371/journal.ppat.1006720
PMID:29125880
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5699845/
Abstract

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 IKKα/β, 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/IKKε by TRAFs that were pre-associated with TBK1/IKKε via direct interaction between the coiled-coil domain of TRAFs and the SDD domain of TBK1/IKKε. 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-κB and TBK1/IKKε activation. NEMO-activated IKKα/β were important for TBK1/IKKε activation through IKKα/β-mediated TBK1/IKKε phosphorylation. Moreover, individual TRAFs differently mediated TBK1/IKKε activation and thus fine-tuned antiviral immunity under physiological conditions.

摘要

线粒体抗病毒信号蛋白（MAVS）在RNA病毒感染后传递来自视黄酸诱导基因I样受体的信号。然而，MAVS激活下游组分（如TBK1和IKKα/β）的机制尚不清楚，尽管先前的研究表明NEMO或TBK1结合蛋白TANK、NAP1和SINTBAD参与其中。在这里，我们报告MAVS介导的先天免疫激活依赖于肿瘤坏死因子受体相关因子（TRAFs），部分依赖于NEMO，但不依赖于TBK1结合蛋白。MAVS通过TRAFs招募TBK1/IKKε，这些TRAFs通过TRAFs的卷曲螺旋结构域与TBK1/IKKε的SDD结构域之间的直接相互作用而预先与TBK1/IKKε结合。TRAF2-/-3-/-5-/-6-/-细胞完全丧失了对RNA病毒的反应。TRAFs的E3连接酶活性通过合成与NEMO结合以激活NF-κB和TBK1/IKKε的泛素链来实现NEMO的激活。NEMO激活的IKKα/β通过IKKα/β介导的TBK1/IKKε磷酸化对TBK1/IKKε的激活很重要。此外，单个TRAFs以不同方式介导TBK1/IKKε的激活，从而在生理条件下微调抗病毒免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/ae2831478cab/ppat.1006720.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/e0bbbab54df2/ppat.1006720.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/067a6a7f9bdb/ppat.1006720.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/002b21bbcfb7/ppat.1006720.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/b4ee33f96cc3/ppat.1006720.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/b209f679fd9f/ppat.1006720.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/4562a4301311/ppat.1006720.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/ae2831478cab/ppat.1006720.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/e0bbbab54df2/ppat.1006720.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/067a6a7f9bdb/ppat.1006720.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/002b21bbcfb7/ppat.1006720.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/b4ee33f96cc3/ppat.1006720.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/b209f679fd9f/ppat.1006720.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/4562a4301311/ppat.1006720.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4704/5699845/ae2831478cab/ppat.1006720.g007.jpg

相似文献

[1]
MAVS activates TBK1 and IKKε through TRAFs in NEMO dependent and independent manner.

PLoS Pathog. 2017-11-10

[2]
PPM1A silences cytosolic RNA sensing and antiviral defense through direct dephosphorylation of MAVS and TBK1.

Sci Adv. 2016-7-1

[3]
MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I interferon production after activation of the antiviral RIG-I-like receptors.

BMC Biol. 2012-5-24

[4]
The Kinase MAP4K1 Inhibits Cytosolic RNA-Induced Antiviral Signaling by Promoting Proteasomal Degradation of TBK1/IKKε.

Microbiol Spectr. 2021-12-22

[5]
DDX3 directly regulates TRAF3 ubiquitination and acts as a scaffold to co-ordinate assembly of signalling complexes downstream from MAVS.

Biochem J. 2017-2-15

[6]
MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades.

Elife. 2013-8-14

[7]
SINTBAD, a novel component of innate antiviral immunity, shares a TBK1-binding domain with NAP1 and TANK.

EMBO J. 2007-7-11

[8]
Porcine Deltacoronavirus Accessory Protein NS7a Antagonizes IFN-β Production by Competing With TRAF3 and IRF3 for Binding to IKKε.

Front Cell Infect Microbiol. 2020-6-12

[9]
Lipopolysaccharide-mediated interferon regulatory factor activation involves TBK1-IKKepsilon-dependent Lys(63)-linked polyubiquitination and phosphorylation of TANK/I-TRAF.

J Biol Chem. 2007-10-26

[10]
THO Complex Subunit 7 Homolog Negatively Regulates Cellular Antiviral Response against RNA Viruses by Targeting TBK1.

Viruses. 2019-2-15

引用本文的文献

[1]
The aryl hydrocarbon receptor interacting protein suppresses RNA virus-induced type I IFN and IL-6 in mouse macrophages.

bioRxiv. 2025-7-2

[2]
The macrophage-intrinsic MDA5/IRF5 axis drives HIV-1 intron-containing RNA-induced inflammatory responses.

J Clin Invest. 2025-6-10

[3]
PWWP3A disrupts the assembly of VISA/MAVS signalosome to inhibit innate immune response against RNA viruses.

Nat Commun. 2025-5-1

[4]
Modeling Necroptotic and Pyroptotic Signaling in .

Biomolecules. 2025-4-4

[5]
ARID5A orchestrates cardiac aging and inflammation through MAVS mRNA stabilization.

Nat Cardiovasc Res. 2025-5

[6]
ARID5A promotes inflammation and fibrosis during cardiac aging.

Nat Cardiovasc Res. 2025-5

[7]
Adaptor-Mediated Trafficking of Tank Binding Kinase 1 During Diverse Cellular Processes.

Traffic. 2025

[8]
Exploring the role of oral bacteria in oral cancer: a narrative review.

Discov Oncol. 2025-2-26

[9]
ARIES domains: functional signaling units of type I interferon responses.

FEBS J. 2025-2-18

[10]
Cellular RNA interacts with MAVS to promote antiviral signaling.

Science. 2024-12-20

本文引用的文献

[1]
Structural Insights into mitochondrial antiviral signaling protein (MAVS)-tumor necrosis factor receptor-associated factor 6 (TRAF6) signaling.

J Biol Chem. 2015-10-30

[2]
Correction: Structural basis for the prion-like MAVS filaments in antiviral innate immunity.

Elife. 2015-8-28

[3]
Identification and characterization of phosphodiesterases that specifically degrade 3'3'-cyclic GMP-AMP.

Cell Res. 2015-5

[4]
Identification and characterization of MAVS from black carp Mylopharyngodon piceus.

Fish Shellfish Immunol. 2015-4

[5]
Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation.

Science. 2015-1-29

[6]
Molecular imprinting as a signal-activation mechanism of the viral RNA sensor RIG-I.

Mol Cell. 2014-7-10

[7]
Structural basis for the prion-like MAVS filaments in antiviral innate immunity.

Elife. 2014-1-1

[8]
MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades.

Elife. 2013-8-14

[9]
TRAF molecules in cell signaling and in human diseases.

J Mol Signal. 2013-6-13

[10]
Genome editing with RNA-guided Cas9 nuclease in zebrafish embryos.

Cell Res. 2013-3-26

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索