FoxO1 Negatively Regulates Cellular Antiviral Response by Promoting Degradation of IRF3

被引：65

作者：

Lei, Cao-Qi ^{[1
]}

Zhang, Yu ^{[1
]}

Xia, Tian ^{[1
]}

Jiang, Li-Qun ^{[1
]}

Zhong, Bo ^{[1
]}

Shu, Hong-Bing ^{[1
]}

机构：

[1] Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Peoples R China

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2013年 / 288卷 / 18期

基金：

美国国家科学基金会;

关键词：

NF-KAPPA-B; I INTERFERON; ADAPTER PROTEIN; TRANSCRIPTION FACTORS; ACTIVATION; PHOSPHORYLATION; UBIQUITINATION; IDENTIFICATION; RECOGNITION; MECHANISMS;

D O I：

10.1074/jbc.M112.444794

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：

Viral infection causes activation of the transcription factor IRF3, which is critical for production of type I interferons (IFNs) and innate antiviral immune response. How virus-induced type I IFN signaling is controlled is not fully understood. Here we identified the transcription factor FoxO1 as a negative regulator for virus-triggered IFN-beta induction. Overexpression of FoxO1 inhibited virus-triggered ISRE activation, IFN-beta induction as well as cellular antiviral response, whereas knockdown of FoxO1 had opposite effects. FoxO1 interacted with IRF3 in a viral infection-dependent manner and promoted K48-linked polyubiquitination and degradation of IRF3 in the cytosol. Furthermore, FoxO1-mediated degradation of IRF3 was independent of the known E3 ubiquitin ligases for IRF3, including RBCK1 and RAUL. Our findings thus suggest that FoxO1 negatively regulates cellular antiviral response by promoting IRF3 ubiquitination and degradation, providing a previously unknown mechanism for control of type I IFN induction and cellular antiviral response.

引用

页码：12596 / 12604

页数：9

共 31 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] IDENTIFICATION OF A MEMBER OF THE INTERFERON REGULATORY FACTOR FAMILY THAT BINDS TO THE INTERFERON-STIMULATED RESPONSE ELEMENT AND ACTIVATES EXPRESSION OF INTERFERON-INDUCED GENES [J].

AU, WC ;

MOORE, PA ;

LOWTHER, W ;

JUANG, YT ;

PITHA, PM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (25) :11657-11661

[4] FoxO proteins in insulin action and metabolism [J].

Barthel, A ;

Schmoll, D ;

Unterman, TG .

TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2005, 16 (04) :183-189

[5] FOXO transcription factors at the interface between longevity and tumor suppression [J].

Greer, EL ;

Brunet, A .

ONCOGENE, 2005, 24 (50) :7410-7425

[6] 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

[7] Convergence of the NF-κB and IRF pathways in the regulation of the innate antiviral response [J].

Hiscott, John .

CYTOKINE & GROWTH FACTOR REVIEWS, 2007, 18 (5-6) :483-490

[8] STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling [J].

Ishikawa, Hiroki ;

Barber, Glen N. .

NATURE, 2008, 455 (7213) :674-U74

[9] IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction [J].

Kawai, T ;

Takahashi, K ;

Sato, S ;

Coban, C ;

Kumar, H ;

Kato, H ;

Ishii, KJ ;

Takeuchi, O ;

Akira, S .

NATURE IMMUNOLOGY, 2005, 6 (10) :981-988

[10] Virus infection triggers SUMOylation of IRF3 and IRF7, leading to the negative regulation of type I interferon gene expression [J].

Kubota, Toru ;

Matsuoka, Mayumi ;

Chang, Tsung-Hsien ;

Tailor, Prafullakumar ;

Sasaki, Tsuguo ;

Tashiro, Masato ;

Kato, Atsushi ;

Ozato, Keiko .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (37) :25660-25670

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