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cGAS-STING信号通路激活机制和细胞功能研究概述
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Abstract:
cGAS-STING信号通路是先天免疫的重要通路之一，其由环磷酸鸟苷-磷酸腺苷酸合成酶(cyclic GMP-AMP synthase, cGAS)、干扰素基因刺激物(stimulator of interferon gene, STING)和一系列下游信号转导接头分子及效应分子共同组成。环GMP-AMP合成酶(cGAS)可以识别细菌、病毒等微生物的核酸，进而可以催化环GMP-AMP (cGAMP)的合成，激活免疫应答，通过STING-TBK1信号通路刺激I型干扰素的诱导。然而，该cGAS-STING信号通路还与多种疾病的发生有关，其异常激活可能使机体引发自身免疫性疾病。在细胞水平上，cGAS-STING信号通路的多方面作用已经出现：这些作用包括自噬、翻译、新陈代谢平衡、DNA损伤修复、衰老和细胞凋亡。这些作用由关键的通路成分及其与细胞生理状态的内在联系所致。在这篇综述中，我们将讨论由cGAS-STING信号通路控制的细胞生理状态的最新进展、与疾病的相关性以及引起疾病的内在机制。本文旨在提供一个全面的信号通路信息框架，结合这些机制以及细胞功能的发现，帮助研究人员更好地了解cGAS-STING信号通路的细胞功能，从而发现一些有前景的疾病治疗靶点，为今后的研究奠定理论基础。
The cGAS-STING signaling pathway is one of the important pathways in innate immunity, which consists of cyclic GMP-AMP synthase (cGAS), stimulator of interferon gene (STING) and a series of downstream signaling junction molecules and effectors molecules. Cyclic GMP-AMP synthase (cGAS) recognizes nucleic acids from bacteria, viruses, and other microorganisms, which in turn catalyzes the synthesis of cyclic GMP-AMP (cGAMP), activates the immune response, and stimulates the induction of type I interferon through the STING-TBK1 signaling pathway. However, this cGAS-STING signaling pathway has also been implicated in the development of a variety of diseases, and its aberrant activation may allow the body to trigger autoimmune diseases. At the cellular level, multifaceted roles for the cGAS-STING signaling pathway have emerged: these include autophagy, translation, metabolic homeostasis, DNA damage repair, senescence, and apoptosis. These roles result from key pathway components and their intrinsic connection to the physiological state of the cell. In this review, we will discuss recent advances in cellular physiological states controlled by the cGAS-STING signaling pathway, their relevance to disease, and the intrinsic mechanisms that cause disease. The aim of this paper is to provide a comprehensive framework of signaling pathway information, combined with the discovery of these mechanisms as well as cellular functions, to help researchers better understand the cellular functions of the cGAS-STING signaling pathway, which will lead to the discovery of some promising therapeutic targets for diseases, and lay a theoretical foundation for future research.
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