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The tumor suppressor PTEN has a critical role in antiviral innate immunity.
- Source :
-
Nature immunology [Nat Immunol] 2016 Mar; Vol. 17 (3), pp. 241-9. Date of Electronic Publication: 2015 Dec 21. - Publication Year :
- 2016
-
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.
- Subjects :
- 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
Immunoblotting
Immunoprecipitation
Interferon Regulatory Factor-3 genetics
Interferon Regulatory Factor-7 genetics
MCF-7 Cells
Macrophages immunology
Mass Spectrometry
Mice
Microscopy, Confocal
Mutagenesis, Site-Directed
PTEN Phosphohydrolase genetics
Phosphatidylinositol 3-Kinases metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sendai virus
Vesiculovirus
Immunity, Innate immunology
Interferon Regulatory Factor-3 immunology
Interferon Type I immunology
PTEN Phosphohydrolase immunology
Respirovirus Infections immunology
Rhabdoviridae Infections immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 17
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 26692175
- Full Text :
- https://doi.org/10.1038/ni.3311