The Adaptor Protein MITA Links Virus-Sensing Receptors to IRF3 Transcription Factor Activation

被引：1313

作者：

Zhong, Bo ^{[1
]}

Yang, Yan ^{[1
]}

Li, Shu ^{[1
]}

Wang, Yan-Yi ^{[1
]}

Li, Ying ^{[1
]}

Diao, Feici ^{[1
]}

Lei, Caoqi ^{[1
]}

He, Xiao ^{[1
]}

Zhang, Lu ^{[1
]}

Tien, Po ^{[1
]}

Shu, Hong-Bing ^{[1
]}

机构：

[1] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China

来源：

IMMUNITY | 2008年 / 29卷 / 04期

基金：

中国国家自然科学基金;

关键词：

D O I：

10.1016/j.immuni.2008.09.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Viral infection triggers activation of transcription factors such as NF-kappa B and IRF3, which collaborate to induce type I interferons (IFNs) and elicit innate antiviral response. Here, we identified MITA as a critical mediator of virus-triggered type I IFN signaling by expression cloning. Overexpression of MITA activated IRF3, whereas knockdown of MITA inhibited virus-triggered activation of IRF3, expression of type I IFNs, and cellular antiviral response. MITA was found to localize to the outer membrane of mitochondria and to be associated with VISA, a mitochondrial protein that acts as an adaptor in virus-triggered signaling. MITA also interacted with IRF3 and recruited the kinase TBK1 to the VISA-associated complex. MITA was phosphorylated by TBK1, which is required for MITA-mediated activation of IRF3. Our results suggest that MITA is a critical mediator of virus-triggered IRF3 activation and IFN expression and further demonstrate the importance of certain mitochondrial proteins in innate antiviral immunity.

引用

页码：538 / 550

页数：13

共 47 条

[1] Pathogen recognition and innate immunity [J].

Akira, S ;

Uematsu, S ;

Takeuchi, O .

CELL, 2006, 124 (04) :783-801

[2] Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 [J].

Alexopoulou, L ;

Holt, AC ;

Medzhitov, R ;

Flavell, RA .

NATURE, 2001, 413 (6857) :732-738

[3] The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-β promoter [J].

Andrejeva, J ;

Childs, KS ;

Young, DF ;

Carlos, TS ;

Stock, N ;

Goodbourn, S ;

Randall, RE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (49) :17264-17269

[4] Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125 [J].

Arimoto, Kei-ichiro ;

Takahashi, Hitoshi ;

Hishiki, Takayuki ;

Konishi, Hicleyuki ;

Fujita, Takashi ;

Shimotohno, Kunitada .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (18) :7500-7505

[5] Negative regulation of MDA5-but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase [J].

Diao, Feici ;

Li, Shu ;

Tian, Yang ;

Zhang, Min ;

Xu, Liang-Guo ;

Zhang, Yan ;

Wang, Rui-Peng ;

Chen, Danying ;

Zhai, Zhonghe ;

Zhong, Bo ;

Tien, Po ;

Shu, Hong-Bing .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (28) :11706-11711

[6] Type IIFN modulates innate and specific antiviral immunity [J].

Durbin, JE ;

Fernandez-Sesma, A ;

Lee, CK ;

Rao, TD ;

Frey, AB ;

Moran, TM ;

Vukmanovic, S ;

García-Sastre, A ;

Levy, DE .

JOURNAL OF IMMUNOLOGY, 2000, 164 (08) :4220-4228

[7] IKKε and TBK1 are essential components of the IRF3 signaling pathway [J].

Fitzgerald, KA ;

McWhirter, SM ;

Faia, KL ;

Rowe, DC ;

Latz, E ;

Golenbock, DT ;

Coyle, AJ ;

Liao, SM ;

Maniatis, T .

NATURE IMMUNOLOGY, 2003, 4 (05) :491-496

[8] TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity [J].

Gack, Michaela U. ;

Shin, Young C. ;

Joo, Chul-Hyun ;

Urano, Tomohiko ;

Liang, Chengyu ;

Sun, Lijun ;

Takeuchi, Osamu ;

Akira, Shizuo ;

Chen, Zhijian ;

Inoue, Satoshi ;

Jung, Jae U. .

NATURE, 2007, 446 (7138) :916-U2

[9] Mechanisms of the TRIF-induced interferon-stimulated response element and NF-κB activation and apoptosis pathways [J].

Han, KJ ;

Su, XQ ;

Xu, LG ;

Bin, LH ;

Zhang, J ;

Shu, HB .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (15) :15652-15661

[10] The roles of two IκB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection [J].

Hemmi, H ;

Takeuchi, O ;

Sato, S ;

Yamamoto, M ;

Kaisho, T ;

Sanjo, H ;

Kawai, T ;

Hoshino, K ;

Takeda, K ;

Akira, S .

JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (12) :1641-1650

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