期刊
CELLULAR SIGNALLING
卷 24, 期 11, 页码 2197-2204出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2012.06.017
关键词
PPM1B; TBK1; Phosphatase; Antiviral response
类别
资金
- NIH/NINDS [1R01NS072420-01]
- Virginia & L E Simmons Family Foundation Collaborative Research Fund
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.
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