Article
Immunology
Wanxin Zhuang, Lei Zhang, Yi Zheng, Bingyu Liu, Chunhong Ma, Wei Zhao, Suxia Liu, Feng Liu, Chengjiang Gao
Summary: Inflammasomes are crucial for the innate immune system, and dysregulation of their activation can have negative impacts on human health. This study reveals that USP3 acts as a key regulator of ASC ubiquitination, enhancing its stability and promoting inflammasome activation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
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
Fisheries
Wenxian Zhu, Yuqiang Cheng, Zhaofei Wang, Likai Ji, Jingjiao Ma, Yaxian Yan, Hengan Wang, Jianhe Sun
Summary: Compared with mammals, chickens have an impaired innate immune system with key genes inactivated or missing. A predicted N-terminal deletion in the chicken Cyclic GMP-AMP synthase gene has been experimentally confirmed, but further experimental evidence is needed to verify its functional integrity.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Caixia Liu, Jingyi Yang, Jiaxin Zheng, Jianmian Fu, Weisi Wang, Liping Duan, Xuhong Qian, Yangyang Yang
Summary: Phase separation is a critical biophysical process that allows biomolecules to form membraneless compartments in response to cellular stimuli. Recently, phase separation has been observed in immune signaling pathways, such as the cGAS-STING pathway, and its association with pathological processes like viral infections, cancers, and inflammatory diseases has been highlighted. This review discusses the role of phase separation in cGAS-STING signaling and its cellular regulatory functions, as well as therapeutic strategies targeting this pathway in cancer progression.
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)
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.
Article
Multidisciplinary Sciences
Haiyan Gu, Jing Yang, Jiayu Zhang, Ying Song, Yao Zhang, Pengfei Xu, Yuanxiang Zhu, Liangliang Wang, Pengfei Zhang, Lin Li, Dahua Chen, Qinmiao Sun
Summary: cGAS is regulated by its interacting protein PCBP2, which controls its enzyme activity and affects cGAS-STING signaling pathway in antiviral response. Overexpression of PCBP2 reduces the antiviral signaling while loss of PCBP2 increases cGAS activity. PCBP2 decreases cGAS enzyme activity by antagonizing cGAS condensation, ensuring appropriate cGAMP production and balanced cGAS-STING signal transduction.
NATURE COMMUNICATIONS
(2022)
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
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.
Article
Biochemistry & Molecular Biology
Hua Guan, Wen Zhang, Dafei Xie, Yuehua Nie, Shi Chen, Xiaoya Sun, Hongling Zhao, Xiaochang Liu, Hua Wang, Xin Huang, Chenjun Bai, Bo Huang, Pingkun Zhou, Shanshan Gao
Summary: Mitochondria is a vital organelle affected by ionizing radiation (IR) outside the nucleus. This study investigates the impact and role of cytosolic mitochondrial DNA (mtDNA) and associated cGAS signaling on hematopoietic injury caused by IR in both in vitro and in vivo models. The findings reveal that IR exposure promotes the release of mtDNA into the cytosol, activating the cGAS signaling pathway. Furthermore, inhibiting VDAC1 and cGAS synthetase can mitigate bone marrow injury and ameliorate hematopoietic suppression induced by IR. This research provides insights into the non-target effects of radiation and offers a potential strategy for preventing and treating hematopoietic acute radiation syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Wen Zhou, Lisa Mohr, John Maciejowski, Philip J. Kranzusch
Summary: The phase separation of cGAS-DNA is critical for efficient sensing of immunostimulatory DNA, as it limits the activity of the cytosolic exonuclease TREX1. This selective environment suppresses TREX1 function and restricts DNA degradation, balancing cytosolic DNA degradation and innate immune activation.
Article
Multidisciplinary Sciences
Manuel Adrian Suter, Nikki Y. Tan, Chung Hwee Thiam, Muznah Khatoo, Paul A. MacAry, Veronique Angeli, Stephan Gasser, Y. L. Zhang
Summary: Deficiencies in DNA repair and nucleases lead to cytosolic DNA accumulation. The cGAS-STING pathway is important for detecting cytosolic DNA, but its function can be modulated by IL-6 and JAK2/STAT3 signaling pathways in cancer cells, affecting interferon expression and tumor rejection.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Tetsuya Yoshimoto, Mizuho Kittaka, Andrew Anh Phuong Doan, Rina Urata, Matthew Prideaux, Roxana E. Rojas, Clifford Harding, W. Henry Boom, Lynda F. Bonewald, Edward M. Greenfield, Yasuyoshi Ueki
Summary: In the context of periodontal infection, the MYD88 pathway in osteocytes plays a dominant role in regulating osteolysis caused by bacterial infection. Matrix-embedded osteocytes stimulated with bacterial pathogen-associated molecular patterns (PAMPs) directly drive bone resorption through an MYD88-regulated signaling pathway. Mice lacking MYD88 primarily in osteocytes protect against bone loss caused by bacterial PAMPs injections and resist alveolar bone resorption induced by oral Porphyromonas gingivalis (Pg) infection. Targeted restoration of MYD88 in osteocytes leads to osteolysis with inflammatory cell infiltration. In vitro, bacterial PAMPs induce higher expression of the cytokine RANKL in osteocytes compared to osteoblasts. Activation of the osteocyte MYD88 pathway up-regulates RANKL by increasing binding of transcription factors CREB and STAT3 to Rankl enhancers and suppressing K48-ubiquitination of CREB/CREB binding protein and STAT3. Blocking MYD88 prevents jawbone loss in Pg-driven periodontitis. These findings suggest that MYD88 and downstream RANKL regulators in osteocytes are potential therapeutic targets for osteolysis in periodontitis and osteomyelitis.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Qiang Guo, Ximiao Chen, Jiaoxiang Chen, Gang Zheng, Chenglong Xie, Hongqiang Wu, Zhimin Miao, Yan Lin, Xiangyang Wang, Weiyang Gao, Xiangtao Zheng, Zongyou Pan, Yifei Zhou, Yaosen Wu, Xiaolei Zhang
Summary: The study investigated the role of STING in osteoarthritis progression, revealing its involvement in ECM metabolism, apoptosis, and senescence in chondrocytes. STING activation of NF-kappa B signaling cascade was found to contribute to OA development, with suppression of STING showing potential as a therapeutic approach.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Xintao Tu, Ting-Ting Chu, Devon Jeltema, Kennady Abbott, Kun Yang, Cong Xing, Jie Han, Nicole Dobbs, Nan Yan
Summary: This study reveals that interference with STING trafficking can trigger basal activation of interferon signaling, providing protection against infection. GCC2 and several RAB GTPases are identified as key regulators during the post-Golgi trafficking of STING. These findings suggest the potential of exploiting this mechanism for cancer immunotherapy.
NATURE COMMUNICATIONS
(2022)
Review
Microbiology
Fanhua Wei, Chengjiang Gao, Yujiong Wang
Summary: Influenza virus infection can lead to cytokine storms, contributing to severe outcomes. Immunomodulatory drugs offer a promising approach for treating hypercytokinemia induced by acute viral infections.
CRITICAL REVIEWS IN MICROBIOLOGY
(2022)
Article
Immunology
Chao Sui, Tongyang Xiao, Shengyuan Zhang, Hongxiang Zeng, Yi Zheng, Bingyu Liu, Gang Xu, Chengjiang Gao, Zheng Zhang
Summary: This study reveals that SARS-CoV-2 inhibits the host interferon response by using NSP13 to recruit TBK1 for autophagic degradation. The findings provide new insights into the transmission and pathogenesis of SARS-CoV-2 infection.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Virology
Lulu Han, Yi Zheng, Jian Deng, Mei-Ling Nan, Yang Xiao, Meng-Wei Zhuang, Jing Zhang, Wei Wang, Chengjiang Gao, Pei-Hui Wang
Summary: A characteristic feature of COVID-19 is the dysregulated immune response and overwhelming inflammatory cytokine storm. This study demonstrates that the ORF10 protein of SARS-CoV-2 interacts with STING, impairing the cGAS-STING signaling pathway and weakening the innate antiviral immunity.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Review
Microbiology
Yi Zheng, Chengjiang Gao
Summary: SARS-CoV-2 poses a threat to human health and the global economy, but effective treatments are still lacking. Recent studies suggest that phase separation plays a critical role in regulating antiviral signaling and viral replication, highlighting its significance in virus-host interaction.
Article
Virology
Jian Deng, Sheng-Nan Zheng, Yang Xiao, Mei-Ling Nan, Jing Zhang, Lulu Han, Yi Zheng, Yanying Yu, Qiang Ding, Chengjiang Gao, Pei-Hui Wang
Summary: SARS-CoV-2 NSP8 inhibits the production of type I and III interferons by targeting RIG-I/MDA5, TRIF, and STING signaling molecules. It disrupts the assembly of RIG-I/MDA5-MAVS complex, resulting in impaired phosphorylation and nuclear translocation of IRF3. NSP8 also directly interacts with TRIF and STING to suppress their signaling transduction.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Virology
Jian Deng, Yi Zheng, Sheng-Nan Zheng, Mei-Ling Nan, Lulu Han, Jing Zhang, Yunyun Jin, Ji-An Pan, Chengjiang Gao, Pei-Hui Wang
Summary: The NSP7 protein of SARS-CoV-2 inhibits the production of interferons, crucial components of antiviral immunity, by targeting multiple signaling pathways. It disrupts the normal functioning of RIG-I/MDA5, TLR3-TRIF, and cGAS-STING pathways, leading to a dampened interferon response. Additionally, NSP7 decreases immune activation and facilitates virus replication.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Mutian Jia, Yuanyuan Wang, Jie Wang, Danhui Qin, Mengge Wang, Li Chai, Yue Fu, Chunyuan Zhao, Chengjiang Gao, Jihui Jia, Wei Zhao
Summary: This study demonstrates that STING-triggered autophagy plays a crucial role in eliminating pathogens and limiting STING-induced interferon responses. Specifically, myristic acid attenuates IFN responses while enhancing STING-dependent autophagy, contributing to immune homeostasis. Mechanistically, myristic acid promotes N-myristoylation of ARF1, which controls STING membrane trafficking and enhances autophagy degradation of the STING complex. Targeting myristic acid and N-myristoylation could be a promising approach for treating diseases caused by aberrant STING activation.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Lingli Kong, Chao Sui, Tian Chen, Lei Zhang, Wei Zhao, Yi Zheng, Bingyu Liu, Xiaochen Cheng, Chengjiang Gao
Summary: Researchers have identified TRIM10 as a positive regulator of STING signaling, showing that it enhances the STING-dependent type I interferon response by promoting STING aggregation and interaction with TBK1. TRIM10-deficient cells and mice are more susceptible to viral infections and exhibit faster melanoma growth.
Article
Immunology
Feng Liu, Wanxin Zhuang, Bin Song, Yuan Yang, Junqi Liu, Yi Zheng, Bingyu Liu, Jie Zheng, Wei Zhao, Chengjiang Gao
Summary: In this study, the researchers discovered that K63-linked polyubiquitin chains loaded on MAVS can be recognized by RIG-I to initiate MAVS aggregation. They also identified Ube2N as a major enzyme involved in the polyubiquitination of MAVS and found that it cooperates with Riplet and TRIM31 to promote unanchored polyubiquitination. Additionally, they identified USP10 as a deubiquitinating enzyme that removes unanchored polyubiquitin chains from MAVS.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Immunology
Yi Zheng, Xuejing Zhang, Chengjiang Gao
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Immunology
Wanxin Zhuang, Lei Zhang, Yi Zheng, Bingyu Liu, Chunhong Ma, Wei Zhao, Suxia Liu, Feng Liu, Chengjiang Gao
Summary: Inflammasomes are crucial for the innate immune system, and dysregulation of their activation can have negative impacts on human health. This study reveals that USP3 acts as a key regulator of ASC ubiquitination, enhancing its stability and promoting inflammasome activation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Biochemical Research Methods
Zhenzhen Yan, Hansen Liu, Chengjiang Gao
Summary: This article presents a protocol for detecting the aggregation of TBK1 upon viral infection using HSV-1 infected mouse peritoneal macrophages, which can be adapted for other proteins and viruses.
Article
Biochemistry & Molecular Biology
Yi Zheng, Jian Deng, Lulu Han, Meng-Wei Zhuang, Yanwen Xu, Jing Zhang, Mei-Ling Nan, Yang Xiao, Peng Zhan, Xinyong Liu, Chengjiang Gao, Pei-Hui Wang
Summary: This study reveals the involvement of the stress response pathway and innate antiviral immunity in the pathogenic mechanism of SARS-CoV-2. NSP5 and N protein of SARS-CoV-2 were found to attenuate the formation of antiviral stress granules (avSG). NSP5 suppressed avSG formation and disrupted the RIG-I-MAVS complex to weaken the RIG-I-mediated antiviral response, while N protein specifically targeted cofactors upstream of RIG-I and affected the recognition of dsRNA by RIG-I.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
