title: The tumor suppressor PTEN has a critical role in antiviral innate immunity.
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.
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Ruangang
authors.initials: R
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Cao
authors.affiliation: Medical Research Institute, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
authors.forename: Shuliang
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Cao-Qi
authors.initials: CQ
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Li
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Eija
authors.initials: E
authors.lastname: Jokitalo
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
authors.affiliation: 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.
authors.forename: Deyin
authors.initials: D
authors.lastname: Guo
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology*; D050839:Interferon Regulatory Factor-7 / Q000235:genetics; D007370:Interferon Type I / Q000276:immunology*; D061986:MCF-7 Cells; D008264:Macrophages / Q000276:immunology; D013058:Mass Spectrometry; D051379:Mice; D018613:Microscopy, Confocal; D016297:Mutagenesis, Site-Directed; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D010253:Respirovirus Infections / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018353:Rhabdoviridae Infections / Q000276:immunology*; D029082:Sendai virus; D018116:Vesiculovirus
chemical_list: D016207:Cytokines; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; C494235:Irf7 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase