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Nat Immunol. 2016 Mar;17(3):241-9. doi: 10.1038/ni.3311. Epub 2015 Dec 21.

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

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State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
Medical Research Institute, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.


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-╬▓ 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.

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