Review
Biochemistry & Molecular Biology
Le Yu, Pengda Liu
Summary: cGAS is a major cytosolic DNA sensor that, when hyperactivated, contributes to autoimmune diseases but serves as an adjuvant for anticancer immune therapy; inactivation of cGAS signaling causes difficulty in sensing and clearing infections, as well as facilitating tumor immune evasion, therefore cGAS activation is tightly controlled.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Multidisciplinary Sciences
Yu-Lin Yang, Li -Bo Cao, Wen-Rui He, Li Zhong, Yi Guo, Qing Yang, Hong -Bing Shu, Ming-Ming Hu
Summary: The current understanding of nucleic acid-mediated innate immunity is that the binding of intracellular sensors to nucleic acids is enough to activate them. However, this study reveals that the endocytosis of viruses or foreign DNA provides a priming signal for the activation of the DNA sensor cGAS in the innate immune response. This finding demonstrates that the activation of cGAS following endocytosis requires tyrosine phosphorylation mediated by the V-ATPase-SYK pathway.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Chen-Yang Liao, Cao-Qi Lei, Hong-Bing Shu
Summary: PCBP1 is an important factor in promoting cGAS activation and binding to viral DNA. Deficiency of PCBP1 can inhibit the innate immune response triggered by cytosolic DNA and DNA viruses.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Review
Cell Biology
Juli Bai, Feng Liu
Summary: cGAS plays a crucial role as a DNA sensor in the cytosol and nucleus, with potential additional functions beyond DNA sensing in the nucleus that are still poorly understood.
Article
Cell Biology
Hong Sun, Yu Huang, Shan Mei, Fengwen Xu, Xiaoman Liu, Fei Zhao, Lijuan Yin, Di Zhang, Liang Wei, Chao Wu, Shichao Ma, Jianwei Wang, Shan Cen, Chen Liang, Siqi Hu, Fei Guo
Summary: cGAS is localized in both the cytoplasm and nucleus, demonstrating a functional nuclear export signal for its positioning between the nucleus and cytoplasm. Mutation of the key amino acid L172 results in the loss of interferon response to DNA stimulation.
Review
Biochemistry & Molecular Biology
Thomas J. Hayman, Peter M. Glazer
Summary: Research on disease treatment has focused on DNA repair pathways, with potential for enhanced efficacy with novel immunotherapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Wen-Rui He, Li-Bo Cao, Yu-Lin Yang, Duo Hua, Ming-Ming Hu, Hong-Bing Shu
Summary: The study identified VRK2 as a key regulator of mtDNA release in response to mitochondrial stress, viral infection, and nonviral factors causing Ca2+ overload. VRK2 plays a crucial role in triggering the cGAS-mediated innate immune response and may serve as a potential therapeutic target for infectious and autoimmune diseases associated with mtDNA release.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Eliana M. Barros, Stuart A. McIntosh, Kienan I. Savage
Summary: Genomic instability is a hallmark of tumourigenesis, and defects in the DNA damage response (DDR) play a crucial role in shaping therapeutic response. The cGAS/STING signalling pathway has been identified as a key mediator of inflammation in response to DNA damage. Multiple DNA repair defects and DNA damage induced by conventional chemotherapy/radiation can also activate the innate immune response through cGAS/STING activation. Combining DNA damaging agents with immunotherapies has potential therapeutic opportunities.
Article
Virology
Yulin Xu, Youwen Zhang, Shaohua Sun, Jia Luo, Sen Jiang, Jiajia Zhang, Xueliang Liu, Qi Shao, Qi Cao, Wanglong Zheng, Nanhua Chen, Francois Meurens, Jianzhong Zhu
Summary: The cGAS-STING signal plays an important antiviral role in PRRSV infection, as demonstrated by the suppression of infection with stable expression of STING or stimulation of cGAS-STING signaling, while the knockout of STING gene increases the level of infection.
Article
Cell Biology
Ravi Shankar Singh, Venkatasubramanian Vidhyasagar, Shizhuo Yang, Ananna Bhadra Arna, Manisha Yadav, Aanchal Aggarwal, Alexya N. Aguilera, Satoru Shinriki, Kalpana Kalyanasundaram Bhanumathy, Kannupriya Pandey, Aizhang Xu, Noreen Rapin, Mark Bosch, John DeCoteau, Jim Xiang, Franco J. Vizeacoumar, Yan Zhou, Vikram Misra, Hirotaka Matsui, Susan R. Ross, Yuliang Wu
Summary: The DDX41 protein plays a crucial role in the activation of the cGAS-STING pathway, which is responsible for the production of type I interferon after DNA virus infection. DDX41 regulates cGAS and STING activation, and its mutant form, R525H, shows enhanced cGAS activity. The findings suggest that DDX41 functions by unwinding and annealing DNA to maintain the balance of dsDNA and ssDNA, thus regulating cGAS-STING activation.
Review
Cell Biology
Zhilei Wang, Nian Chen, Zhiyong Li, Guang Xu, Xiaoyan Zhan, Jianyuan Tang, Xiaohe Xiao, Zhaofang Bai
Summary: Inflammation is a protective response regulated by the host, with cGAS-STING pathway playing a crucial role in immune defense, viral infections, fatty liver, and cancer metastasis. The potential impact of this pathway in liver diseases has attracted widespread attention, with pharmacological agonists and antagonists offering new therapeutic possibilities. Understanding the mechanisms of cGAS-STING pathway may lead to the development of effective treatments for liver diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fei Wang, Mengmeng Zhao, Boran Chang, Yilong Zhou, Xiangyang Wu, Mingtong Ma, Siyu Liu, Yajuan Cao, Mengge Zheng, Yifang Dang, Junfang Xu, Li Chen, Tianhao Liu, Fen Tang, Yefei Ren, Zhu Xu, Zhiyong Mao, Kai Huang, Minhua Luo, Jinsong Li, Haipeng Liu, Baoxue Ge
Summary: Virus infection induces DNA damage and activates PARP1, which interacts with cGAS in the cytoplasm to inhibit antiviral immunity.
Review
Cell Biology
Mansour Akbari, Daryl P. Shanley, Vilhelm A. Bohr, Lene Juel Rasmussen
Summary: Aging is caused by lifelong accumulation of random damage to cells and tissues, leading to increased innate immunity markers and low-grade chronic inflammation. Activation of the DNA sensing cGAS-STING signaling pathway by misplaced cytosolic self-DNA may result in chronic inflammation and characteristics of the aging process.
Review
Immunology
Ximing Jin, Wenjia Wang, Xinwei Zhao, Wenhua Jiang, Qingqing Shao, Zhuo Chen, Cong Huang
Summary: The incidence of human herpesvirus (HHVs) is increasing and has impacted a wide range of population. The cGAS-STING pathway plays a crucial role in human diseases, particularly in HHV infections, and viruses have evolved strategies to evade this pathway to escape immune detection. The modulation of the cGAS-STING pathway has become a potential therapeutic target for the development of antiviral drugs and vaccines, as well as the investigation of disease models related to this pathway.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Shasha Chen, Zhiyong Liao, Pinglong Xu
Summary: Mitochondria play versatile roles in cellular processes and have emerged as critical components in innate immunity. This review provides a comprehensive exploration of the multifaceted mechanisms underlying the interactions between mitochondria and innate immune responses. It discusses the roles of healthy mitochondria as platforms for signalosome assembly, the release of mitochondrial components as signaling messengers, and the regulation of signaling via mitophagy. Additionally, it explores the impacts of mitochondrial proteins and metabolites on modulating innate immune responses, immune cell polarization, and their implications in infectious and inflammatory diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Correction
Immunology
Saskia F. Erttmann, Anetta Hartlova, Marta Sloniecka, Faizal A. M. Raffi, Ava Hosseinzadeh, Tomas Edgren, Reza Rofougaran, Ulrike Resch, Maria Fallman, Torben Ek, Nelson O. Gekara
Editorial Material
Cell Biology
Nelson O. Gekara
JOURNAL OF CELL BIOLOGY
(2017)
Article
Microbiology
Steve J. Webster, Sven Brode, Lou Ellis, Timothy J. Fitzmaurice, Matthew J. Elder, Nelson O. Gekara, Panagiotis Tourlomousis, Clare Bryant, Simon Clare, Ronnie Chee, Hill J. S. Gaston, Jane C. Goodall
Article
Multidisciplinary Sciences
Swarupa Panda, Nelson O. Gekara
NATURE COMMUNICATIONS
(2018)
Article
Biochemistry & Molecular Biology
Hui Jiang, Xiaoyu Xue, Swarupa Panda, Ajinkya Kawale, Richard M. Hooy, Fengshan Liang, Jungsan Sohn, Patrick Sung, Nelson O. Gekara
Article
Multidisciplinary Sciences
Saskia F. Erttmann, Nelson O. Gekara
NATURE COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Pilar Samperio Ventayol, Petra Geiser, Maria Letizia Di Martino, Alexandra Florbrant, Stefan A. Fattinger, Naemi Walder, Eduardo Sima, Feng Shao, Nelson O. Gekara, Magnus Sundbom, Wolf-Dietrich Hardt, Dominic-Luc Webb, Per M. Hellstrom, Jens Eriksson, Mikael E. Sellin
Summary: The study found that infection with Salmonella Typhimurium triggers focal contractions in intestinal epithelial cells, which are initiated by the NAIP/NLRC4 inflammasome and can prevent infected cell death and expulsion, thereby protecting the integrity of the intestinal epithelium.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Hui Jiang, Patrycja Swacha, Nelson O. Gekara
Summary: Mice lacking ALRs are resistant to radiation-induced BM injury, as nuclear ALRs act as inhibitors of DNA repair, accelerating genome destabilization, micronuclei generation, and cell death. The study uncovers ALRs as potential targets for interventions against genotoxic tissue injury and as potential biomarkers for predicting the outcome of radio/chemotherapy.
Article
Biochemical Research Methods
Saskia F. Erttmann, Nelson O. Gekara
Summary: This article describes a protocol for enriching bacterial membrane vesicles from serum and colon, which can be adapted for other tissues. The protocol involves pre-clearing serum or colon fluids using 0.2-mm syringe filters, concentrating the vesicles using centrifugal filter devices, isolating the vesicles with qEV size exclusion columns, and concentrating the isolated vesicle fractions for downstream analyses. For more detailed information on the use and execution of this protocol, please refer to Erttmann et al. (2022).
Letter
Cell Biology
Hui Jiang, Patrycja Swacha, Kyaw Min Aung, Nelson O. Gekara
Article
Cell Biology
Daniela Putzova, Swarupa Panda, Anetta Hartlova, Jiri Stulik, Nelson O. Gekara
CELLULAR MICROBIOLOGY
(2017)