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环鸟苷酸-腺苷酸合成酶在癌症预防中的作用

Cyclic GMP-AMP Synthase in Cancer Prevention.

作者信息

Chen Weidong, Lee Ga-Eun, Jeung Dohyun, Byun Jiin, Juan Wu, Cho Yong-Yeon

机构信息

BK21-Four, College of Pharmacy, The Catholic University of Korea.

RCD Control Material Research Institute, The Catholic University of Korea, Bucheon, Korea.

出版信息

J Cancer Prev. 2023 Dec 30;28(4):143-196. doi: 10.15430/JCP.2023.28.4.143.

Abstract

Cyclic GMP-AMP (cGAMP), synthesized by cGAMP synthase (cGAS), serves as a secondary messenger that modulates various cellular processes, including cell proliferation, cell death, immune response, and inflammation. cGAS is activated upon detecting cytoplasmic DNA, which may originate from damaged genomic and mitochondrial DNA or from viral and bacterial infections. The presence of DNA in the cytoplasm can trigger a substantial inflammatory reaction and cytokine production via the cGAS-STING signaling pathway. Consequently, specific inhibitors targeting this pathway hold significant potential as chemopreventive agents. In this review, we explore the potential effectiveness of modulating cGAS activity. We discuss the role of cGAMP, the mechanism of action for distinguishing between self and foreign DNA, and the possible functions of cGAS within the nucleus.

摘要

环状GMP-AMP(cGAMP)由cGAMP合酶(cGAS)合成,作为第二信使调节各种细胞过程,包括细胞增殖、细胞死亡、免疫反应和炎症。cGAS在检测到细胞质DNA时被激活,这些DNA可能源自受损的基因组和线粒体DNA,或来自病毒和细菌感染。细胞质中DNA的存在可通过cGAS-STING信号通路引发大量炎症反应和细胞因子产生。因此,靶向该通路的特异性抑制剂作为化学预防剂具有巨大潜力。在本综述中,我们探讨调节cGAS活性的潜在有效性。我们讨论了cGAMP的作用、区分自身和外来DNA的作用机制以及cGAS在细胞核内的可能功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c885/10774482/e23da7d687f2/jcp-28-4-143-f1.jpg

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