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

Shun Li; Mingzhu Zhu; Ruangang Pan; Ting Fang; Yuan-Yuan Cao; Shuliang Chen; Xiaolu Zhao; Cao-Qi Lei; Lin Guo; Yu Chen; Chun-Mei Li; Eija Jokitalo; Yuxin Yin; Hong-Bing Shu; Deyin Guo

doi:10.1038/ni.3311

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

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

Authors

Shun Li¹, Mingzhu Zhu¹, Ruangang Pan¹, Ting Fang¹, Yuan-Yuan Cao¹, Shuliang Chen², Xiaolu Zhao¹, Cao-Qi Lei¹, Lin Guo¹, Yu Chen¹, Chun-Mei Li³, Eija Jokitalo³, Yuxin Yin⁴, Hong-Bing Shu¹, Deyin Guo^{1

2}

Affiliations

¹ State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
² Medical Research Institute, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
³ Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
⁴ Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

PMID: 26692175
DOI: 10.1038/ni.3311

Abstract

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-β 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cell Line, Tumor
Cell Nucleus
Cell Proliferation
Cytokines / immunology
Dendritic Cells / immunology
Electrophoresis, Polyacrylamide Gel
Fluorescent Antibody Technique
Gene Transfer Techniques
HEK293 Cells
Humans
Immunity, Innate / immunology*
Immunoblotting
Immunoprecipitation
Interferon Regulatory Factor-3 / genetics
Interferon Regulatory Factor-3 / immunology*
Interferon Regulatory Factor-7 / genetics
Interferon Type I / immunology*
MCF-7 Cells
Macrophages / immunology
Mass Spectrometry
Mice
Microscopy, Confocal
Mutagenesis, Site-Directed
PTEN Phosphohydrolase / genetics
PTEN Phosphohydrolase / immunology*
Phosphatidylinositol 3-Kinases / metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism
Respirovirus Infections / immunology*
Reverse Transcriptase Polymerase Chain Reaction
Rhabdoviridae Infections / immunology*
Sendai virus
Vesiculovirus

Substances

Cytokines
Interferon Regulatory Factor-3
Interferon Regulatory Factor-7
Interferon Type I
Irf7 protein, mouse
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
PTEN Phosphohydrolase