Zhang Mengyuan, Wu Changxin, Lu Defen, Wang Xing, Shang Guijun
Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, China.
Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, China.
Sci China Life Sci. 2025 Jan 14. doi: 10.1007/s11427-024-2808-3.
The cGAS-STING pathway plays a crucial role in the innate immune system by detecting mislocalized double-stranded DNA (dsDNA) in the cytoplasm and triggering downstream signal transduction. Understanding the mechanisms by which cGAS and STING operate is vital for gaining insights into the biology of this pathway. This review provides a detailed examination of the structural features of cGAS and STING proteins, with a particular emphasis on their activation and inhibition mechanisms. We also discuss the novel discovery of STING functioning as an ion channel. Furthermore, we offer an overview of key agonists and antagonists of cGAS and STING, shedding light on their mechanisms of action. Deciphering the molecular intricacies of the cGAS-STING pathway holds significant promise for the development of targeted therapies aimed at maintaining immune homeostasis within both innate and adaptive immunity.
环鸟苷酸-腺苷酸合成酶-干扰素基因刺激蛋白(cGAS-STING)通路通过检测细胞质中定位错误的双链DNA(dsDNA)并触发下游信号转导,在先天免疫系统中发挥关键作用。了解cGAS和STING的作用机制对于深入认识该通路的生物学特性至关重要。本综述详细研究了cGAS和STING蛋白的结构特征,尤其着重于它们的激活和抑制机制。我们还讨论了STING作为离子通道的新发现。此外,我们概述了cGAS和STING的关键激动剂和拮抗剂,并阐明了它们的作用机制。破解cGAS-STING通路的分子复杂性对于开发旨在维持先天免疫和适应性免疫内免疫稳态的靶向治疗具有重大前景。