The tumor suppressor PTEN has a critical role in antiviral innate immunity

被引：150

作者：

Li, Shun ^{[1
,2
]}

Zhu, Mingzhu ^{[1
,2
]}

Pan, Ruangang ^{[1
,2
]}

Fang, Ting ^{[1
,2
]}

Cao, Yuan-Yuan ^{[1
,2
]}

Chen, Shuliang ^{[3
]}

Zhao, Xiaolu ^{[1
,2
]}

Lei, Cao-Qi ^{[1
,2
]}

Guo, Lin ^{[1
,2
]}

Chen, Yu ^{[1
,2
]}

Li, Chun-Mei ^{[4
]}

Jokitalo, Eija ^{[4
]}

Yin, Yuxin ^{[5
]}

Shu, Hong-Bing ^{[1
,2
]}

Guo, Deyin ^{[1
,2
,3
]}

机构：

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

[2] Wuhan Univ, Coll Life Sci, Modern Virol Res Ctr, Wuhan 430072, Peoples R China

[3] Wuhan Univ, Sch Basic Med Sci, Med Res Inst, Wuhan 430072, Peoples R China

[4] Univ Helsinki, Inst Biotechnol, Helsinki, Finland

[5] Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pathol, Beijing 100871, Peoples R China

来源：

NATURE IMMUNOLOGY | 2016年 / 17卷 / 03期

基金：

中国国家自然科学基金;

关键词：

INTERFERON REGULATORY FACTOR-3; DOUBLE-STRANDED-RNA; PATTERN-RECOGNITION RECEPTORS; TOLL-LIKE RECEPTORS; TRANSCRIPTION FACTORS; DENDRITIC CELLS; NUCLEAR IMPORT; I INTERFERON; NEGATIVE REGULATION; GENE INDUCTION;

D O I：

10.1038/ni.3311

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The gene encoding PTEN is one of the most frequently mutated tumor suppressor-encoding genes in human cancer. While PTEN's function in tumor suppression is well established, its relationship to anti-microbial immunity remains unknown. Here we found a pivotal role for PTEN in the induction of type I interferon, the hallmark of antiviral innate immunity, that was independent of the pathway of the kinases PI(3)K and Akt. PTEN controlled the import of IRF3, a master transcription factor responsible for IFN-beta production, into the nucleus. We further identified a PTEN-controlled negative phosphorylation site at Ser97 of IRF3 and found that release from this negative regulation via the phosphatase activity of PTEN was essential for the activation of IRF3 and its import into the nucleus. Our study identifies crosstalk between PTEN and IRF3 in tumor suppression and innate immunity.

引用

页码：241 / 249

页数：9

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