MDA5 is SUMOylated by PIAS2β in the upregulation of Type I interferon signaling

被引：47

作者：

Fu, Jihuan ^{[1
,2
]}

Xiong, Yanbao ^{[1
,2
]}

Xu, Youli ^{[1
]}

Cheng, Genhong ^{[1
,3
]}

Tang, Hong ^{[1
]}

机构：

[1] Chinese Acad Sci, Key Lab Infect & Immun, Inst Biophys, Beijing 100101, Peoples R China

[2] Chinese Acad Sci, Grad Univ, Beijing 100080, Peoples R China

[3] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

来源：

MOLECULAR IMMUNOLOGY | 2011年 / 48卷 / 04期

关键词：

SUMOylation; IFNs; MDA5; Ubiquitylation; NF-KAPPA-B; STAT1-MEDIATED GENE ACTIVATION; NEGATIVE FEEDBACK-REGULATION; E3 UBIQUITIN LIGASE; SUMO-BINDING MOTIF; RIG-I; ADAPTER PROTEIN; RNA HELICASE; RECOGNITION; VIRUS;

D O I：

10.1016/j.molimm.2010.09.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Retinoic acid-inducible protein I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are cytosolic viral RNA sensors that induce type I interferon production (IFN). In this study, we found that MDA5 undergoes inducible SUMOylation by small ubiquitin-like modifier-1 (SUMO-1) in response to polyI:C stimulation. Enhanced SUMOylation of MDA5 by exogenously expressed SUMO-conjugating enzyme Ubc9 correlated with upregulation of IFN expression and repressed virus replication. Conversely, overexpression of a SUMOylation-deficient mutant of Ubc9 or knockdown of endogenous Ubc9 reduced IFN production. Furthermore, we showed that PIAS2 beta, a SUMOylation E3 ligase, could specifically interact with and enhance the SUMOylation of MDA5. Consequently, PIAS2 beta knockdown reduced the SUMOylation of MDA5 and the IFN production. Collectively, these findings suggest that SUMO-1 modification of MDA5 possibly via PIAS2 beta may play a role in the MDA5-mediated IFN response to viral infections. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：415 / 422

页数：8

共 61 条

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

Akira, S ;

Uematsu, S ;

Takeuchi, O .

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

[2] 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

[3] 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

[4] Principles of ubiquitin and SUMO modifications in DNA repair [J].

Bergink, Steven ;

Jentsch, Stefan .

NATURE, 2009, 458 (7237) :461-467

[5] p53-Ubl fusions as models of ubiquitination, sumoylation and neddylation of p53 [J].

Carter, Stephanie ;

Vousden, Karen H. .

CELL CYCLE, 2008, 7 (16) :2519-2528

[6] SUMO-1 modification of IκBα inhibits NF-κB activation [J].

Desterro, JMP ;

Rodriguez, MS ;

Hay, RT .

MOLECULAR CELL, 1998, 2 (02) :233-239

[7] The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response [J].

Friedman, Constantin S. ;

O'Donnell, Marie Anne ;

Legarda-Addison, Diana ;

Ng, Aylwin ;

Cardenas, Washington B. ;

Yount, Jacob S. ;

Moran, Thomas M. ;

Basler, Christopher F. ;

Komuro, Akihiko ;

Horvath, Curt M. ;

Xavier, Ramnik ;

Ting, Adrian T. .

EMBO REPORTS, 2008, 9 (09) :930-936

[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] REUL Is a Novel E3 Ubiquitin Ligase and Stimulator of Retinoic-Acid-Inducible Gene-I [J].

Gao, Dong ;

Yang, Yong-Kang ;

Wang, Rui-Peng ;

Zhou, Xiang ;

Diao, Fei-Ci ;

Li, Min-Dian ;

Zhai, Zhong-He ;

Jiang, Zheng-Fan ;

Chen, Dan-Ying .

PLOS ONE, 2009, 4 (06)

[10] Essential role of mda-5 in type IIFN responses to polyriboinosinic: polyribocytidylic acid and encephalomyocarditis picornavirus [J].

Gitlin, Leonid ;

Barchet, Winfried ;

Gilfillan, Susan ;

Cella, Marina ;

Beutler, Bruce ;

Flavell, Richard A. ;

Diamond, Michael S. ;

Colonna, Marco .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (22) :8459-8464

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