Central Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Research Center of Translational Medicine, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
Front Immunol. 2024 Mar 7;15:1380517. doi: 10.3389/fimmu.2024.1380517. eCollection 2024.
As a canonical cytoplasmic DNA sensor, cyclic GMP-AMP synthase (cGAS) plays a key role in innate immunity. In recent years, a growing number of studies have shown that cGAS can also be located in the nucleus and plays new functions such as regulating DNA damage repair, nuclear membrane repair, chromosome fusion, DNA replication, angiogenesis and other non-canonical functions. Meanwhile, the mechanisms underlying the nucleo-cytoplasmic transport and the regulation of cGAS activation have been revealed in recent years. Based on the current understanding of the structure, subcellular localization and canonical functions of cGAS, this review focuses on summarizing the mechanisms underlying nucleo-cytoplasmic transport, activity regulation and non-canonical functions of cGAS in the nucleus. We aim to provide insights into exploring the new functions of cGAS in the nucleus and advance its clinical translation.
作为一种规范的细胞质 DNA 传感器，环鸟苷酸-腺苷酸合酶（cGAS）在先天免疫中发挥着关键作用。近年来，越来越多的研究表明 cGAS 也可以位于细胞核中，并发挥调节 DNA 损伤修复、核膜修复、染色体融合、DNA 复制、血管生成等非规范功能。同时，近年来也揭示了 cGAS 核质转运和激活调节的机制。基于目前对 cGAS 的结构、亚细胞定位和规范功能的理解，本综述重点总结了 cGAS 在细胞核中的核质转运、活性调节和非规范功能的机制。我们旨在为探索 cGAS 在细胞核中的新功能并推进其临床转化提供思路。
