PCBP1 modulates the innate immune response by facilitating the binding of cGAS to DNA
PCBP1 modulates the innate immune response by facilitating the binding of cGAS to DNA
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PCBP1 通过促进 cGAS 与 DNA 的结合来调节先天免疫反应
DOI：
10.1038/s41423-020-0462-3
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发表时间：
2020-05-15
影响因子：
24.1
通讯作者：
Shu, Hong-Bing
中科院分区：
文献类型：
--
作者：
Liao, Chen-Yang;Lei, Cao-Qi;Shu, Hong-Bing
环GMP-AMP合酶（cGAS）是识别胞质溶胶中DNA的关键传感器，并催化第二信使环GMP-AMP（cGAMP）的合成，其结合衔接蛋白MITA（也称为STING、MPYS和ERIS）以启动先天性免疫应答。DNA与cGAS的结合和cGAS的激活如何被调节仍然知之甚少。使用生化纯化方法，我们确定聚（rC）结合蛋白1（PCBP 1）作为cGAS相关蛋白。PCBP 1以病毒感染依赖性方式募集至cGAS。PCBP 1直接与DNA结合，并增强cGAS与其配体的结合，这对cGAS活化很重要。因此，PCBP 1缺陷抑制胞质DNA和DNA病毒触发的下游效应基因的转录。这些发现表明PCBP 1通过促进cGAS与病毒DNA的结合在cGAS介导的对DNA病毒感染的先天免疫应答中起重要作用。
Cyclic GMP-AMP synthase (cGAS) is a key sensor critical for the recognition of DNA in the cytosol and catalyzes the synthesis of the second messenger cyclic GMP-AMP (cGAMP), which binds to the adapter protein MITA (also known as STING, MPYS, and ERIS) to initiate the innate immune response. How the binding of DNA to and the activation of cGAS are regulated remains poorly understood. Using a biochemical purification approach, we identified poly(rC)-binding protein 1 (PCBP1) as a cGAS-associated protein. PCBP1 was recruited to cGAS in a viral infection-dependent manner. PCBP1 directly bound to DNA and enhanced cGAS binding to its ligands, which was important for cGAS activation. Consistently, PCBP1 deficiency inhibited cytosolic DNA- and DNA virus-triggered transcription of downstream effector genes. These findings suggest that PCBP1 plays an important role in the cGAS-mediated innate immune response to DNA virus infection by promoting the binding of cGAS to viral DNA.