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环鸟苷酸-腺苷酸合成酶(cGAS)和 STING 信号通路在炎症和感染中的调控作用。

Regulation of cGAS and STING signaling during inflammation and infection.

机构信息

Departments of Medicine and Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Departments of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA.

出版信息

J Biol Chem. 2023 Jul;299(7):104866. doi: 10.1016/j.jbc.2023.104866. Epub 2023 May 27.

Abstract

Stimulator of interferon genes (STING) is a sensor of cyclic dinucleotides including cyclic GMP-AMP, which is produced by cyclic GMP-AMP synthase (cGAS) in response to cytosolic DNA. The cGAS-STING signaling pathway regulates both innate and adaptive immune responses, as well as fundamental cellular functions such as autophagy, senescence, and apoptosis. Mutations leading to constitutive activation of STING cause devastating human diseases. Thus, the cGAS-STING pathway is of great interest because of its role in diverse cellular processes and because of the potential therapeutic implications of targeting cGAS and STING. Here, we review molecular and cellular mechanisms of STING signaling, and we propose a framework for understanding the immunological and other cellular functions of STING in the context of disease.

摘要

干扰素基因刺激物 (STING) 是环二核苷酸的传感器,包括环鸟苷酸-腺苷酸 (cyclic GMP-AMP),它是由环鸟苷酸-AMP 合酶 (cGAS) 产生的,以响应细胞溶质 DNA。cGAS-STING 信号通路调节先天和适应性免疫反应,以及自噬、衰老和细胞凋亡等基本细胞功能。导致 STING 组成性激活的突变会导致毁灭性的人类疾病。因此,cGAS-STING 途径因其在多种细胞过程中的作用以及靶向 cGAS 和 STING 的潜在治疗意义而备受关注。在这里,我们回顾了 STING 信号的分子和细胞机制,并提出了一个框架,用于理解 STING 在疾病背景下的免疫和其他细胞功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9963/10316007/30fa822b57ea/gr1.jpg

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