Translational control of the activation of transcription factor NF-κB and production of type I interferon by phosphorylation of the translation factor eIF4E

被引：103

作者：

Herdy, Barbara ^{[1
,2
]}

Jaramillo, Maritza ^{[1
,2
]}

Svitkin, Yuri V. ^{[1
,2
]}

Rosenfeld, Amy B. ^{[1
,2
]}

Kobayashi, Mariko ^{[3
,4
]}

Walsh, Derek ^{[6
]}

Alain, Tommy ^{[1
,2
]}

Sean, Polen ^{[1
,2
]}

Robichaud, Nathaniel ^{[1
,2
]}

Topisirovic, Ivan ^{[1
,2
]}

Furic, Luc ^{[5
]}

Dowling, Ryan J. O. ^{[1
,2
]}

Sylvestre, Annie ^{[1
,2
]}

Rong, Liwei ^{[7
]}

Colina, Rodney ^{[8
]}

Costa-Mattioli, Mauro ^{[9
]}

Fritz, Joerg H. ^{[10
,11
]}

Olivier, Martin ^{[11
,12
]}

Brown, Earl ^{[13
,14
]}

Mohr, Ian ^{[3
,4
]}

Sonenberg, Nahum ^{[1
,2
]}

机构：

[1] McGill Univ, Dept Biochem, Montreal, PQ, Canada

[2] McGill Univ, Goodman Canc Res Ctr, Montreal, PQ, Canada

[3] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA

[4] NYU, Sch Med, NYU Canc Inst, New York, NY USA

[5] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic, Australia

[6] Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland

[7] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, McGill AIDS Ctr, Montreal, PQ H3T 1E2, Canada

[8] Univ Republ, Reg Norte Salto, Mol Virol Lab, Salto, Uruguay

[9] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA

[10] McGill Univ, Complex Traits Grp, Montreal, PQ, Canada

[11] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada

[12] McGill Univ, Ctr Study Host Resistance, McGill Univ Hlth Ctr, Res Inst,Dept Med, Montreal, PQ, Canada

[13] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada

[14] Univ Ottawa, Emerging Pathogens Res Ctr, Ottawa, ON, Canada

来源：

NATURE IMMUNOLOGY | 2012年 / 13卷 / 06期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

INITIATION-FACTOR; 4E; BINDING PROTEIN EIF4E; EUKARYOTIC TRANSLATION; SIGNALING PATHWAYS; NITRIC-OXIDE; BETA; DEPHOSPHORYLATION; REDISTRIBUTION; INVOLVEMENT; INHIBITION;

D O I：

10.1038/ni.2291

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Type I interferon is an integral component of the antiviral response, and its production is tightly controlled at the levels of transcription and translation. The eukaryotic translation-initiation factor eIF4E is a rate-limiting factor whose activity is regulated by phosphorylation of Ser209. Here we found that mice and fibroblasts in which eIF4E cannot be phosphorylated were less susceptible to virus infection. More production of type I interferon, resulting from less translation of Nfkbia mRNA (which encodes the inhibitor I kappa B alpha), largely explained this phenotype. The lower abundance of IkBa resulted in enhanced activity of the transcription factor NF-kappa B, which promoted the production of interferon-beta (IFN-beta). Thus, regulated phosphorylation of eIF4E has a key role in antiviral host defense by selectively controlling the translation of an mRNA that encodes a critical suppressor of the innate antiviral response.

引用

页码：543 / +

页数：10

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