Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 15, Issue 1, Pages 48-57Publisher
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/cmi.2017.102
Keywords
antiviral responses; innate immunity; PTEN; PTEN-L; type I interferon
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Funding
- National Nature Science Foundation of China [81620108020]
- China '973' Basic Research Program [2013CB911101]
- Hubei Provincial Science & Technology Innovation Team [2015CFA009]
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Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a well-known tumor suppressor that acts as a dual-specificity phosphatase and is frequently mutated in human cancer. Our previous work has demonstrated that PTEN also plays a vital role in type I interferon responses and antiviral innate immunity. Recently, a translational variant of PTEN with a long N-terminal extension (PTEN-L) has been discovered that is secreted into the extracellular environment and enters recipient cells, where it exerts a phosphatase function antagonistic to PI3K/Akt signaling and tumorigenesis. In this study, we demonstrate that PTEN-L promotes type I interferon responses and antiviral innate immunity during viral infection in a phosphatase activity-dependent manner. Compared with canonical PTEN, PTEN-L also exerts its antiviral function when it is applied exogenously in protein form. This finding was confirmed in cell cultures and mouse infection models. Furthermore, PTEN-L enhances the responses of both type I interferon and proinflammatory cytokines, thus suggesting that PTEN-L might possess additional functions compared with those of PTEN. Thus, the antiviral function of PTEN-L may open an avenue for the use of PTEN-L in antiviral therapy, particularly in patients with PTEN-deficient tumors.
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