Cell Reports (Dec 2018)
The Cyclopeptide Astin C Specifically Inhibits the Innate Immune CDN Sensor STING
- Senlin Li,
- Ze Hong,
- Zhe Wang,
- Fei Li,
- Jiahao Mei,
- Lulu Huang,
- Xiwen Lou,
- Simeng Zhao,
- Lihua Song,
- Wei Chen,
- Qiang Wang,
- Heng Liu,
- Yanni Cai,
- Huansha Yu,
- Huimin Xu,
- Guangzhi Zeng,
- Quanyi Wang,
- Juanjuan Zhu,
- Xing Liu,
- Ninghua Tan,
- Chen Wang
Affiliations
- Senlin Li
- State Key Laboratory of Natural Medicines, School of Life Science and Technology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China; State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
- Ze Hong
- State Key Laboratory of Natural Medicines, School of Life Science and Technology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China
- Zhe Wang
- State Key Laboratory of Natural Medicines, School of Life Science and Technology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China
- Fei Li
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China
- Jiahao Mei
- State Key Laboratory of Natural Medicines, School of Life Science and Technology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China
- Lulu Huang
- State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
- Xiwen Lou
- Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China
- Simeng Zhao
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China
- Lihua Song
- State Key Laboratory of Natural Medicines, School of Life Science and Technology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China
- Wei Chen
- State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
- Qiang Wang
- State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
- Heng Liu
- State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
- Yanni Cai
- State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
- Huansha Yu
- State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
- Huimin Xu
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China
- Guangzhi Zeng
- State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China
- Quanyi Wang
- State Key Laboratory of Natural Medicines, School of Life Science and Technology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China
- Juanjuan Zhu
- State Key Laboratory of Natural Medicines, School of Life Science and Technology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China
- Xing Liu
- Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; Corresponding author
- Ninghua Tan
- State Key Laboratory of Natural Medicines, School of Life Science and Technology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China; Corresponding author
- Chen Wang
- State Key Laboratory of Natural Medicines, School of Life Science and Technology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, China; State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 12
pp. 3405 – 3421.e7
Abstract
Summary: cGAS-STING signaling is essential for innate immunity. Its misregulation promotes cancer or autoimmune and autoinflammatory diseases, and it is imperative to identify effective lead compounds that specifically downregulate the pathway. We report here that astin C, a cyclopeptide isolated from the medicinal plant Aster tataricus, inhibits cGAS-STING signaling and the innate inflammatory responses triggered by cytosolic DNAs. Moreover, mice treated with astin C are more susceptible to HSV-1 infection. Consistently, astin C markedly attenuates the autoinflammatory responses in Trex1−/− BMDM cells and in Trex1−/− mouse autoimmune disease model. Mechanistically, astin C specifically blocks the recruitment of IRF3 onto the STING signalosome. Collectively, this study characterizes a STING-specific small-molecular inhibitor that may be applied for potentially manipulating the STING-mediated clinical diseases. : Li et al. have characterized a small-molecule cyclopeptide, astin C, which specifically inhibits cGAS-STING signaling as well as the innate inflammatory responses. This finding provides a way to potentially manipulate STING-mediated clinical diseases. Keywords: cGAS, STING, IRF3, TBK1, HSV-1, cyclopeptide, astin C, therapeutic target, innate immunity, autoimmune diseases
