https://scholars.lib.ntu.edu.tw/handle/123456789/586012
標題: | The transmembrane serine protease hepsin suppresses type I interferon induction by cleaving STING | 作者: | Hsin, Fu Hsu, Yu-Chen Tsai, Yu-Fei SHU-WHA LIN HELENE MINYI LIU |
公開日期: | 15-六月-2021 | 卷: | 14 | 期: | 687 | 來源出版物: | Science signaling | 摘要: | Many viral proteases mediate the evasion of antiviral innate immunity by cleaving adapter proteins in the interferon (IFN) induction pathway. Host proteases are also involved in innate immunity and inflammation. Here, we report that the transmembrane protease hepsin (also known as TMPRSS1), which is predominantly present in hepatocytes, inhibited the induction of type I IFN during viral infections. Knocking out hepsin in mouse embryonic fibroblasts (MEFs) increased the viral infection-induced expression of Ifnb1, an Ifnb1 promoter reporter, and an IFN-sensitive response element promoter reporter. Ectopic expression of hepsin in cultured human hepatocytes and HEK293T cells suppressed the induction of IFNβ during viral infections by reducing the abundance of STING. These effects depended on the protease activity of hepsin. We identified a putative hepsin target site in STING and showed that mutating this site protected STING from hepsin-mediated cleavage. In addition to hepatocytes, several hepsin-producing prostate cancer cell lines showed reduced STING-mediated type I IFN induction and responses. These results reveal a role for hepsin in suppressing STING-mediated type I IFN induction, which may contribute to the vulnerability of hepatocytes to chronic viral infections. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/586012 | ISSN: | 19450877 | DOI: | 10.1126/scisignal.abb4752 | SDG/關鍵字: | beta interferon; hepsin; interferon; protein; proteinase; stimulator of interferon genes; unclassified drug; hepsin; interferon; serine proteinase; Article; cell culture; cell fractionation; DNA cleavage assay; ectopic expression; gene knockdown; gene kno |
顯示於: | 生物化學暨分子生物學科研究所 |
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