论文
论文题目: PCBP2 maintains antiviral signaling homeostasis by regulating cGAS enzymatic activity via antagonizing its condensation
论文题目英文:
作者: Gu, Haiyan; Yang, Jing; Zhang, Jiayu; Song, Ying; Zhang, Yao; Xu, Pengfei; Zhu, Yuanxiang; Wang, Liangliang; Zhang, Pengfei; Li, Lin; Chen, Dahua; Sun, Qinmiao
论文出处:
年: 2022
卷: 13
期: 1
页:
联系作者: 孙钦秒
发表期刊: Nature Communications
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论文连接 https://www.nature.com/articles/s41467-022-29266-9
影响因子: 17.694
摘要: Cyclic GMP-AMP synthase (cGAS) plays a major role in detecting pathogenic DNA. It produces cyclic dinucleotide cGAMP, which subsequently binds to the adaptor protein STING and further triggers antiviral innate immune responses. However, the molecular mechanisms regulating cGAS enzyme activity remain largely unknown. Here, we characterize the cGAS-interacting protein Poly(rC)-binding protein 2 (PCBP2), which plays an important role in controlling cGAS enzyme activity, thereby mediating appropriate cGAS-STING signaling transduction. We find that PCBP2 overexpression reduces cGAS-STING antiviral signaling, whereas loss of PCBP2 significantly increases cGAS activity. Mechanistically, we show that PCBP2 negatively regulates anti-DNA viral signaling by specifically interacting with cGAS but not other components. Moreover, PCBP2 decreases cGAS enzyme activity by antagonizing cGAS condensation, thus ensuring the appropriate production of cGAMP and balancing cGAS-STING signal transduction. Collectively, our findings provide insight into how the cGAS-mediated antiviral signaling is regulated.
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