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 t...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.展开更多
基金We thank Dr Hong Wu for providing Pten−/−MEFs and Dr Hongliang Li for Ptenflox/flox mice and Dr Mingzhou Chen for providing VSV as a gift.This work was supported by the National Nature Science Foundation of China(grant 81620108020)the China‘973’Basic Research Program(#2013CB911101)Hubei Provincial Science&Technology Innovation Team grant(#2015CFA009).
文摘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.
