SIRT2
锡尔图因
生物
细胞生物学
先天免疫系统
基因
乙酰化
免疫学
遗传学
免疫系统
作者
Yutong Li,Juntao Bie,Song Chen,Yunfei Li,Tianzhuo Zhang,Haishuang Li,Long Zhao,Fuping You,Jianyuan Luo
标识
DOI:10.15252/embr.202357500
摘要
Abstract SIRT2, a cytoplasmic member of the Sirtuin family, has important roles in immunity and inflammation. However, its function in regulating the response to DNA virus infection remains elusive. Here, we find that SIRT2 is a unique regulator among the Sirtuin family that negatively modulates the cGAS‐STING‐signaling pathway. SIRT2 is down‐regulated after Herpes simplex virus‐1 (HSV‐1) infection, and SIRT2 deficiency markedly elevates the expression levels of type I interferon (IFN). SIRT2 inhibits the DNA binding ability and droplet formation of cGAS by interacting with and deacetylating G3BP1 at K257, K276, and K376, leading to the disassembly of the cGAS‐G3BP1 complex, which is critical for cGAS activation. Administration of AGK2, a selective SIRT2 inhibitor, protects mice from HSV‐1 infection and increases the expression of IFN and IFN‐stimulated genes. Our study shows that SIRT2 negatively regulates cGAS activation through G3BP1 deacetylation, suggesting a potential antiviral strategy by modulating SIRT2 activity.
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