Phosphatase Cdc25A Negatively Regulates the Antiviral Immune Response by Inhibiting TBK1 Activity

Journal of Virology
Dandan QiXin Ye

Abstract

The phosphatase Cdc25A plays an important role in cell cycle regulation by dephosphorylating its substrates, such as cyclin-dependent kinases. In this study, we demonstrate that Cdc25A negatively regulates RIG-I-mediated antiviral signaling. We found that ectopic expression of Cdc25A in 293T cells inhibits the activation of beta interferon (IFN-β) induced by Sendai virus and poly(I·C), while knockdown of Cdc25A enhances the transcription of IFN-β stimulated by RNA virus infection. The inhibitory effect of Cdc25A on the antiviral immune response is mainly dependent on its phosphatase activity. Data from a luciferase assay indicated that Cdc25A can inhibit TBK1-mediated activation of IFN-β. Further analysis indicated that Cdc25A can interact with TBK1 and reduce the phosphorylation of TBK1 at S172, which in turn decreases the phosphorylation of its downstream substrate IRF3. Consistently, knockdown of Cdc25A upregulates the phosphorylation of both TBK1-S172 and IRF3 in Sendai virus-infected or TBK1-transfected 293T cells. In addition, we confirmed that Cdc25A can directly dephosphorylate TBK1-S172-p. These results demonstrate that Cdc25A inhibits the antiviral immune response by reducing the active form of TBK1. Using herpes simp...Continue Reading

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Citations

Apr 2, 2019·Expert Opinion on Therapeutic Targets·Chunyuan Zhao, Wei Zhao
Sep 24, 2020·Expert Opinion on Therapeutic Targets·Or-Yam RevachRussell W Jenkins
Mar 20, 2019·Current Opinion in Infectious Diseases·Anjana C KarawitaKirsty R Short
Nov 22, 2020·Nature Communications·Yuhai BiWeifeng Shi
Jan 17, 2021·Communications Biology·Jiahao ZhangWenbao Qi
Jan 19, 2021·Developmental and Comparative Immunology·Hang DengChengyu Hu
Mar 7, 2021·Cancers·Marcelo Ehrlich, Eran Bacharach

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