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学科主题: 临床医学
题名:
PPM1B negatively regulates antiviral response via dephosphorylating TBK1
作者: Zhao, Yanling1,2; Liang, Li3,4; Fan, Yihui1; Sun, Surong5; An, Lei4; Shi, Zhongcheng6; Cheng, Jin1,7; Jia, Wei4,8; Sun, Wenjing1,2; Mori-Akiyama, Yuko6; Zhang, Hong4; Fu, Songbin2; Yang, Jianhua1
关键词: PPM1B ; TBK1 ; Phosphatase ; Antiviral response
刊名: CELLULAR SIGNALLING
发表日期: 2012-11-01
DOI: 10.1016/j.cellsig.2012.06.017
卷: 24, 期:11, 页:2197-2204
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: I-LIKE RECEPTORS ; NF-KAPPA-B ; ADAPTER PROTEIN ; INNATE IMMUNITY ; INTERFERONS ; ACTIVATION ; PATHWAY ; VIRUS ; IRF3 ; AUTOIMMUNITY
英文摘要:

The production of type I interferon must be tightly regulated and aberrant production of type 1 interferon is harmful or even fatal to the host. TBK1 phosphorylation at Ser172 plays an essential role in TBK1-mediated antiviral response. However, how TBK1 activity is negatively regulated remains poorly understood. Using a functional genomics approach, we have identified PPM1B as a TBK1 phosphatase. PPM1B dephosphorylates TBK1 in vivo and in vitro. PPM1B wild-type but not its phosphatase-deficient R179G mutant inhibits TBK1-mediated antiviral response and facilitates VSV replication in the cells. Viral infection induces association of PPM1B with TBK1 in a transient fashion in the cells. Conversely, suppression of PPM1B expression enhances virus-induced IRF3 phosphorylation and IFN beta production. Our study identifies a previously unrecognized role for PPM1B in the negative regulation of antiviral response by acting as a TBK1 phosphatase. (C) 2012 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 1R01NS072420-01
项目资助者: NIH/NINDS ; Virginia &amp ; L E Simmons Family Foundation Collaborative Research Fund
WOS记录号: WOS:000309309100024
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54839
Appears in Collections:北京大学第三临床医学院_期刊论文

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作者单位: 1.Baylor Coll Med, Texas Childrens Canc Ctr, Dept Pediat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA
2.Harbin Med Univ, Med Genet Lab, Harbin 150081, Peoples R China
3.Peking Univ, Dept Tumor Chemotherapy & Radiat Sickness, Hosp 3, Beijing 100191, Peoples R China
4.Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA
5.Xinjiang Univ, Xinjiang Key Lab Biol Resources & Genet Engn, Coll Life Sci & Technol, Urumqi 830046, Peoples R China
6.Baylor Coll Med, Dept Pathol & Immunol, Dan L Duncan Canc Ctr, Houston, TX 77030 USA
7.Peking Univ, Dept Microbiol, Hlth Sci Ctr, Beijing 100191, Peoples R China
8.Shihezi Univ, Dept Pathol, Sch Med, Shihezi 832002, Peoples R China

Recommended Citation:
Zhao, Yanling,Liang, Li,Fan, Yihui,et al. PPM1B negatively regulates antiviral response via dephosphorylating TBK1[J]. CELLULAR SIGNALLING,2012,24(11):2197-2204.
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