IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities
Stimulator of interferon genes (STING) is a crucial innate immune sensor responsible for distinguishing pathogens and cytosolic DNA, mediating innate immune signaling pathways to defend the host. Recent studies have revealed additional regulatory functions of STING beyond its innate immune-related a...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661824000070 |
| _version_ | 1797291817547333632 |
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| author | Xu He Abdalla Wedn Jian Wang Yanlun Gu Hongjin Liu Juqi Zhang Zhiqiang Lin Renpeng Zhou Xiaocong Pang Yimin Cui |
| author_facet | Xu He Abdalla Wedn Jian Wang Yanlun Gu Hongjin Liu Juqi Zhang Zhiqiang Lin Renpeng Zhou Xiaocong Pang Yimin Cui |
| author_sort | Xu He |
| collection | DOAJ |
| description | Stimulator of interferon genes (STING) is a crucial innate immune sensor responsible for distinguishing pathogens and cytosolic DNA, mediating innate immune signaling pathways to defend the host. Recent studies have revealed additional regulatory functions of STING beyond its innate immune-related activities, including the regulation of cellular metabolism, DNA repair, cellular senescence, autophagy and various cell deaths. These findings highlight the broader implications of STING in cellular physiology beyond its role in innate immunity. Currently, approximately 10 STING agonists have entered the clinical stage. Unlike inhibitors, which have a maximum inhibition limit, agonists have the potential for infinite amplification. STING signaling is a complex process that requires precise regulation of STING to ensure balanced immune responses and prevent detrimental autoinflammation. Recent research on the structural mechanism of STING autoinhibition and its negative regulation by adaptor protein complex 1 (AP-1) provides valuable insights into its different effects under physiological and pathological conditions, offering a new perspective for developing immune regulatory drugs. Herein, we present a comprehensive overview of the regulatory functions and molecular mechanisms of STING beyond innate immune regulation, along with updated details of its structural mechanisms. We discuss the implications of these complex regulations in various diseases, emphasizing the importance and feasibility of targeting the immunity-dependent or immunity-independent functions of STING. Moreover, we highlight the current trend in drug development and key points for clinical research, basic research, and translational research related to STING. |
| first_indexed | 2024-03-07T19:42:18Z |
| format | Article |
| id | doaj.art-3144069a7e6c435ab40f7a5760eb2efb |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-07T19:42:18Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-3144069a7e6c435ab40f7a5760eb2efb2024-02-29T05:18:05ZengElsevierPharmacological Research1096-11862024-03-01201107063IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunitiesXu He0Abdalla Wedn1Jian Wang2Yanlun Gu3Hongjin Liu4Juqi Zhang5Zhiqiang Lin6Renpeng Zhou7Xiaocong Pang8Yimin Cui9Institute of Clinical Pharmacology, Peking University First Hospital, Xueyuan Road 38, Haidian District, Beijing 100191, China; Department of Pharmacy, Peking University First Hospital, Xishiku Street, Xicheng District, Beijing 100034, ChinaSchool of Medicine, University of Pittsburgh, 5051 Centre Avenue, Pittsburgh, PA, USADepartment of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, ChinaInstitute of Clinical Pharmacology, Peking University First Hospital, Xueyuan Road 38, Haidian District, Beijing 100191, China; Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Haidian District, Beijing 100191, ChinaDepartment of General Surgery, Peking University First Hospital, Xishiku Street, Xicheng District, Beijing 100034, ChinaInstitute of Clinical Pharmacology, Peking University First Hospital, Xueyuan Road 38, Haidian District, Beijing 100191, China; Department of Pharmacy, Peking University First Hospital, Xishiku Street, Xicheng District, Beijing 100034, ChinaInstitute of Systems Biomedicine, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Anhui 230601, China; Department of Orthopedics and Rehabilitation, Yale University School of Medicine, New Haven CT06519, USA; Corresponding author at: Department of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Anhui 230601, China.Institute of Clinical Pharmacology, Peking University First Hospital, Xueyuan Road 38, Haidian District, Beijing 100191, China; Department of Pharmacy, Peking University First Hospital, Xishiku Street, Xicheng District, Beijing 100034, China; Correspondence to: Department of Pharmacy, Peking University First Hospital, Xishiku Street, Xicheng District, Beijing 100034, China.Institute of Clinical Pharmacology, Peking University First Hospital, Xueyuan Road 38, Haidian District, Beijing 100191, China; Department of Pharmacy, Peking University First Hospital, Xishiku Street, Xicheng District, Beijing 100034, China; Corresponding author at: Institute of Clinical Pharmacology, Peking University First Hospital, Xueyuan Road 38, Haidian District, Beijing 100191, China.Stimulator of interferon genes (STING) is a crucial innate immune sensor responsible for distinguishing pathogens and cytosolic DNA, mediating innate immune signaling pathways to defend the host. Recent studies have revealed additional regulatory functions of STING beyond its innate immune-related activities, including the regulation of cellular metabolism, DNA repair, cellular senescence, autophagy and various cell deaths. These findings highlight the broader implications of STING in cellular physiology beyond its role in innate immunity. Currently, approximately 10 STING agonists have entered the clinical stage. Unlike inhibitors, which have a maximum inhibition limit, agonists have the potential for infinite amplification. STING signaling is a complex process that requires precise regulation of STING to ensure balanced immune responses and prevent detrimental autoinflammation. Recent research on the structural mechanism of STING autoinhibition and its negative regulation by adaptor protein complex 1 (AP-1) provides valuable insights into its different effects under physiological and pathological conditions, offering a new perspective for developing immune regulatory drugs. Herein, we present a comprehensive overview of the regulatory functions and molecular mechanisms of STING beyond innate immune regulation, along with updated details of its structural mechanisms. We discuss the implications of these complex regulations in various diseases, emphasizing the importance and feasibility of targeting the immunity-dependent or immunity-independent functions of STING. Moreover, we highlight the current trend in drug development and key points for clinical research, basic research, and translational research related to STING.http://www.sciencedirect.com/science/article/pii/S1043661824000070STINGCGAS-STING pathwayNovel functionsSTING modulatorsTherapeutic |
| spellingShingle | Xu He Abdalla Wedn Jian Wang Yanlun Gu Hongjin Liu Juqi Zhang Zhiqiang Lin Renpeng Zhou Xiaocong Pang Yimin Cui IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities Pharmacological Research STING CGAS-STING pathway Novel functions STING modulators Therapeutic |
| title | IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities |
| title_full | IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities |
| title_fullStr | IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities |
| title_full_unstemmed | IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities |
| title_short | IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities |
| title_sort | iuphar ecr review the cgas sting pathway novel functions beyond innate immune and emerging therapeutic opportunities |
| topic | STING CGAS-STING pathway Novel functions STING modulators Therapeutic |
| url | http://www.sciencedirect.com/science/article/pii/S1043661824000070 |
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