Tag: cGAS-STING
Activation of cGAS-STING pathway by a mitochondrial DNA-targeted emissive rhodium(III) metallointercalator
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (STING) pathway is a key mediator of innate immunity involved in cancer development and treatment. The roles of mitochondrial DNA (mtDNA) in cancer immunotherapy have been gradually emerged. Herein, we reported a highly emissive rhodium(III) complex (Rh-Mito) as the mtDNA intercalator. Rh-Mito can…
Corrigendum: Crosstalk between cGAS-STING pathway and autophagy in cancer immunity
Published Erratum . 2023 May 19;14:1216456. doi: 10.3389/fimmu.2023.1216456. eCollection 2023. Affiliations Expand Affiliations 1 Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 2 Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 3 Department of Laboratory Medicine, Huadong Hospital, Fudan University, Shanghai,…
Chronic heat stress induces renal fibrosis and mitochondrial dysfunction in laying hens | Journal of Animal Science and Biotechnology
Wasti S, Sah N, Mishra B. Impact of heat stress on poultry health and performances, and potential mitigation strategies. Animals. 2020;10:1266. doi.org/10.3390/ani10081266. Article PubMed PubMed Central Google Scholar Lara LJ, Rostagno MH. Impact of heat stress on poultry production. Animals. 2013;3:356–69. Article PubMed PubMed Central Google Scholar Al-Saffar AA, Rose…
Nano-STING agonist-decorated microrobots boost innate and adaptive anti-tumor immunity
Jerby-Arnon, L.; Shah, P.; Cuoco, M. S.; Rodman, C.; Su, M. J.; Melms, J. C.; Leeson, R.; Kanodia, A.; Mei, S. L.; Lin, J. R. et al. A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade. Cell 2018, 175, 984–997.e24. Article CAS Google Scholar Li, X….
STING-dependent sensing of self-DNA driving pyroptosis contributes to radiation-induced lung injury
Purpose: Radiation therapy (RT) is indispensable for managing thoracic carcinomas. However, its application is limited by radiation-induced lung injury (RILI), one of the most common and fatal complications of thoracic RT. Nonetheless, the exact molecular mechanisms of RILI remain poorly understood. Methods and materials: To elucidate the underlying mechanisms, various…
Regulation of cGAS and STING signaling during inflammation and infection
Review doi: 10.1016/j.jbc.2023.104866. Online ahead of print. Affiliations Expand Affiliations 1 Departments of Medicine and Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104. 2 Departments of Medicine and Microbiology, Departments of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, 63110. 3 Departments of Medicine…
Recently Published Independent Research Reveals New
Results Add to Growing Body of Evidence that Inhibiting PP2A with LB–100 May Be a General Method for Enhancing the Effectiveness of Immunotherapy in Refractory Cancers PASADENA, CA, May 30, 2023 (GLOBE NEWSWIRE) — LIXTE Biotechnology Holdings, Inc. (“LIXTE” or the “Company”) (Nasdaq: LIXT) today announced that a recently published article in the…
cGAS – Ventus Therapeutics
The recognition of foreign nucleic acids inside the cell is a crucial element of the innate immune response. This is accomplished by pattern recognition receptors (PRRs), such as cyclic GMP–AMP synthase (cGAS). cGAS senses intracytoplasmic double-stranded DNA (dsDNA), triggering a cascade that involves the synthesis of the second messenger 2′,3′-cyclic…
Nanodrug Augmenting Antitumor Immunity for Enhanced TNBC Therapy via Pyroptosis and cGAS-STING Activation
doi: 10.1021/acs.nanolett.3c01008. Online ahead of print. Affiliations Expand Affiliations 1 PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China. 2 Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China. 3 Department of Minimally Invasive Interventional Radiology,…
DUSP1 Protects Against Ischemia-Induced Mitochondrial Injury Through Stabilizing mtDNA Via Interaction with JNK by Lang Shi, Hongchu Zha, Zhou Pan, Yao Xia, Huiming Li, Hua Huang, Ruchi Yue, Zhixia Song, Jiefu Zhu :: SSRN
Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check…
The bidirectional roles of the cGAS-STING pathway in pain processing: Cellular and molecular mechanisms
Pain is a common clinical condition. However, the mechanisms underlying pain are not yet fully understood. It is known that the neuroimmune system plays a critical role in the pathogenesis of pain. Recent studies indicated that the cyclic-GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway can activate the innate immune system…
Sting and p53 DNA repair pathways are compromised in Alzheimer’s disease
Vemuri, P. et al. Evaluation of amyloid protective factors and Alzheimer disease neurodegeneration protective factors in elderly individuals. JAMA Neurol. 74(6), 718–726. doi.org/10.1001/jamaneurol.2017.0244 (2017) (Epub 2017/04/19). Article PubMed PubMed Central Google Scholar Soheili-Nezhad, S., van der Linden, R. J., Olde Rikkert, M., Sprooten, E. & Poelmans, G. Long genes are…
Screening and verification of key ubiquitination genes
Introduction Liver cancer is the third most common cause of cancer death globally with hepatocellular carcinoma (HCC) accounting for the majority of liver cancer.1,2 Early HCC (stage I/II) treatment mainly includes radical surgical resection, radiofrequency ablation and liver transplantation.3,4 However, there is a lack of typical clinical symptoms with early-stage…
STING activation in macrophages by vanillic acid exhibits antineoplastic potential
The human immune system is responsible for differentiating between self and non-self, and protects the body from attacks by pathogens and damaged or abnormal cells [1]. Although immunotherapy including immune checkpoint blockade therapy and CAR T cell adoptive immunotherapy has been established as a promising approach for tumor treatment, a…
Inhibition of cGAS aggravated the host inflammatory response to Aspergillus fumigatus
doi: 10.1080/01902148.2023.2211663. Online ahead of print. Affiliations Expand Affiliations 1 Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China. 2 Department of Pathology, College of Basic Medicine, Chongqing Medical University, Chongqing, China. 3 Department of Laboratory Medicine, the First Affiliated Hospital of…
Hallmarks of cardiovascular ageing | Nature Reviews Cardiology
Bergmann, O. et al. Evidence for cardiomyocyte renewal in humans. Science 324, 98–102 (2009). Article CAS PubMed PubMed Central Google Scholar Senyo, S. E. et al. Mammalian heart renewal by pre-existing cardiomyocytes. Nature 493, 433–436 (2013). Article CAS PubMed Google Scholar Bergmann, O. et al. Dynamics of cell generation and…
Potential blood biomarkers for AS identified in study | Proteins could help with diagnosis, monitoring of ankylosing spondylitis
Proteins associated with inflammation and immune system function were identified as potential blood biomarkers for the diagnosis and monitoring of ankylosing spondylitis (AS). “Better biomarkers would address a significant unmet need both in clinic, where earlier diagnosis and referral might be improved, as well as in bettering our understanding of…
MTFP1 loss sensitizes to mtDNA-driven sterile inflammation and heart failure in mice
Author links open overlay panelErminia Donnarumma, Elodie Vimont, Timothy Wai Show more doi.org/10.1016/j.acvdsp.2023.03.070Get rights and content Introduction Mitochondrial integrity is paramount to heart homeostasis. Under certain stress conditions, mitochondrial DNA (mtDNA) can leak into the cytosol and trigger type I innate immunity via the DNA sensing cGAS-STING pathway, the downstream…
The cGAS-STING pathway in diabetic retinopathy and age-related macular degeneration
Review doi: 10.4155/fmc-2022-0301. Online ahead of print. Affiliations Expand Affiliations 1 Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, USA. 2 Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem, NC 27101, USA. Item in Clipboard Review Bo Hu et al. Future Med Chem. 2023….
Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent autophagy pathway activated by TBK1
Attenuation of cGAS-STING signaling is mediated by a p62/SQSTM1-dependent autophagy pathway activated by TBK1 – Fingerprint — University of Texas Southwestern Medical Center Sort by Weight Alphabetically Medicine & Life Sciences Autophagy 57% DNA 33% cyclic guanosine monophosphate-adenosine monophosphate 18% Autophagosomes 14% Second Messenger Systems 13% Inflammation 7% Read more…
African swine fever virus QP383R dampens type I interferon production by promoting cGAS palmitoylation
Cyclic GMP-AMP synthase (cGAS) recognizes viral DNA and synthesizes cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING/MITA) and downstream mediators to elicit an innate immune response. African swine fever virus (ASFV) proteins can antagonize host immune responses to promote its infection. Here, we identified ASFV protein QP383R as…
Harnessing the cooperation between DNA-PK and cGAS in cancer therapies: The cooperation between DNA-PK and cGAS shapes tumour immunogenicity: The cooperation between DNA-PK and cGAS shapes tumour immunogenicity
doi: 10.1002/bies.202300045. Online ahead of print. Affiliations Expand Affiliation 1 IGMM, Université de Montpellier, CNRS, Montpellier, France. Item in Clipboard Clara Taffoni et al. Bioessays. 2023. Show details Display options Display options Format AbstractPubMedPMID doi: 10.1002/bies.202300045. Online ahead of print. Affiliation 1 IGMM, Université de Montpellier, CNRS, Montpellier, France. Item in…
Epigenetic priming improves salvage chemotherapy in diffuse large B-cell lymphoma via endogenous retrovirus-induced cGAS-STING activation | Clinical Epigenetics
5-Azacytidine pretreatment resensitizes cisplatin-resistant DLBCL cell lines to cisplatin to varying degrees A platinum-based anti-neoplastic agent is an essential component of salvage regimens for aggressive lymphomas, for example, rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) for relapsed/refractory DLBCL and Hodgkin lymphoma [21]. As a single agent in humans, cisplatin is administered…
Broad-Spectrum Antivirals Could Stop Pandemics
Credit: matejmo/Getty Images Researchers have identified broad-spectrum antivirals that can act against several families of RNA viruses with pandemic potential. While it is difficult to determine what will cause the next pandemic, the team states in Cell Reports Medicine that viruses born by arthropods are some of the lead candidates….
Activation of the cGAS-STING Pathway by Extra-Nuclear DNA and its Pharmacognostic Modulation in Human Disease
The detection of extranuclear DNA (self or foreign) by Cyclic GMP-AMP synthase (cGAS) is crucial for human health. cGAS triggers the production of the second messenger cyclic guanosine monophosphate (cGMP) upon binding to extranuclear DNA. This, in turn, activates the stimulator of interferon genes (STING) – producing a range…
By Unleashing Microglial cGAS, Tau STINGs Neurons
26 Apr 2023 Springing a leak is rarely good news, but when microglial mitochondria start oozing, it can be particularly bad in situations of tauopathy. So conclude scientists led by Li Gan and Sadaf Amin, Weill Cornell Medicine, New York, in the April 24 Nature Neuroscience. Tau fibrils damage microglial…
Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex
SARS-CoV-2 infection induces mtDNA release and recognition by cGAS Recent studies revealed that SARS-CoV-2 stimulation could cause the accumulation of intracellular and intercellular DNA due to cell fusion, cell death and even tissue damage.17,19,27 To detect SARS-CoV-2-triggered release of DNA during infection, we first detected the cytosolic dsDNA pattern by…
Andrea Ablasser wins Paul Martini Prize 2023
The Paul Martini Foundation promotes drug research and therapy, and facilitates scientific dialogue between medical scientists, research institutions, and health policy representatives. It is named after the renowned scientist and physician, Professor Paul Martini (1889-1964), for his significant contributions to clinical-therapeutic research. Each year, the Foundation awards the Paul Martini…
Nanotherapeutics-Mediated Ferroptosis for Tumor Immunotherapy – Cover Stories – Science Bulletin – Journal
Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway could effectively initiate antitumor immunity, but specific activation of STING pathway is still an enormous challenge. The research team led by Prof. Xian-Zheng Zhang from Wuhan University elaborately developed a ferroptosis-induced mitochondrial DNA (mtDNA)-guided tumor immunotherapy nanoplatform (designated as…
Licorice extract inhibits the cGAS-STING pathway and protects against non-alcoholic steatohepatitis
doi: 10.3389/fphar.2023.1160445. eCollection 2023. Affiliations Expand Affiliations 1 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. 2 Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China. 3 Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. 4…
Cancer research with tremendous promise for breakthroughs
A research team led by Gary Ying Wai Chan from the School of Biological Sciences at The University of Hong Kong (HKU), has revealed the function of a unique enzyme, ANKLE1. ANKLE1 acts on chromatin bridges trapped in the midzone of dividing cells. By cutting these bridges, ANKLE1 prevents damage…
The Crucial Roles and Research Advances of cGAS-STING Pathway in Cutaneous Disorders
Hay, R.J., N.E. Johns, H.C. Williams, et al. 2014. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. The Journal of Investigative Dermatology 134 (6): 1527–1534. Article CAS PubMed Google Scholar Karimkhani, C., R.P. Dellavalle, L.E. Coffeng, et al. 2017. Global…
TREM2 Protects the Brain From Herpes. The Virus Fights Back.
20 Apr 2023 Retroviruses lurking in the human genome aren’t the only potential troublemakers in neurodegenerative diseases (see Part 5 of this series). Herpes simplex virus type 1 (HSV-1) integrates into the genome of trigeminal ganglia nerves, can lie dormant for decades, and flare up as cold sores throughout a person’s…
Scientist to use $200K research grant to seek scleroderma cause | Study to focus on how immune system responses drive disease
The National Scleroderma Foundation has awarded a $200,000 research grant to a University of Minnesota scientist to study how immune system responses drive the emergence of scleroderma — the cause of which remains unknown. The funding for researcher Rafael Contreras-Galindo, PhD, comes in the form of the two-year Marta Marx…
Contreras-Galindo receives grant for research rare diseases treatment – Austin Daily Herald
Contreras-Galindo receives grant for research rare diseases treatment Published 6:21 pm Tuesday, April 18, 2023 Rafael Contreras-Galindo, PhD. Photo provided The Hormel Institute, University of Minnesota’s, Rafael Contreras-Galindo, PhD, has been awarded the Marta Marx Fund for the Eradication of Scleroderma Award from the National Scleroderma Foundation. Scleroderma is a…
Contreras-Galindo receives grant for research rare diseases treatment
Apr. 18—The Hormel Institute, University of Minnesota’s, Rafael Contreras-Galindo, PhD, has been awarded the Marta Marx Fund for the Eradication of Scleroderma Award from the National Scleroderma Foundation. Scleroderma is a group of rare diseases with fewer than 200,000 cases per year and is a serious condition that can be…
Biologists reveal a scissor enzyme that cuts the chromatin bridge and prevents DNA damage and autoimmunity
Knockout of ANKLE1 induces excessive accumulation of cytosolic DNA, leading to activation of immune responses. Credit: Dr Gary Ying Wai Chan and Dr Huadong Jiang A research team led by Dr. Gary Ying Wai Chan from the School of Biological Sciences at The University of Hong Kong (HKU), has revealed…
Borrelia burgdorferi Engages Mammalian Type I IFN Responses via the cGAS-STING Pathway
Borrelia burgdorferi, the etiologic agent of Lyme disease, is a spirochete that modulates numerous host pathways to cause a chronic, multisystem inflammatory disease in humans. B. burgdorferi infection can lead to Lyme carditis, neurologic complications, and arthritis because of the ability of specific borrelial strains to disseminate, invade, and drive…
Responsive manganese-based nanoplatform amplifying cGAS-STING activation for immunotherapy
CITE THIS COLLECTION DataCite3 Biotech3D Printing in Medicine3D Research3D-Printed Materials and Systems4ORAAPG BulletinAAPS OpenAAPS PharmSciTechAbhandlungen aus dem Mathematischen Seminar der Universität HamburgABI Technik (German)Academic MedicineAcademic PediatricsAcademic PsychiatryAcademic QuestionsAcademy of Management DiscoveriesAcademy of Management JournalAcademy of Management Learning and EducationAcademy of Management PerspectivesAcademy of Management ProceedingsAcademy of Management Review He, Qingbin;…
Activation of the cGAS-STING innate immune response in cells with deficient mitochondrial topoisomerase TOP1MT
Abstract The recognition that cytosolic mtDNA activates cGAS-STING innate immune signaling has unlocked novel disease mechanisms. Here, an uncharacterized variant predicted to affect TOP1MT function, P193L, was discovered in a family with multiple early-onset autoimmune diseases, including Systemic Lupus Erythematosus (SLE). Although there was no previous genetic association between TOP1MT…
ProteomeXchange Dataset PXD024088
PXD024088 is an original dataset announced via ProteomeXchange. Dataset Summary Title Neddylation modification on cGAS of human and mouse Description The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) has emerged as a fundamental component fueling the anti-pathogen immunity. Because of its pivotal role in initiating innate immune response, the…
Phase Separation in cGAS-STING Signaling: cytosolic DNA sensing and regulatory functions
. 2023 Apr 11;e202300147. doi: 10.1002/cbic.202300147. Online ahead of print. Affiliations Expand Affiliations 1 East China University of Science and Technology, School of Pharmacy, CHINA. 2 Chinese Center for Disease Control and Prevention, National Institute of Parasitic Diseases, CHINA. 3 East China University of Science and Technology, School of Pharmacy,…
STING recruits WIPI2 for autophagosome formation
doi: 10.1080/15548627.2023.2202108. Online ahead of print. Affiliations Expand Affiliation 1 Department of Biochemistry, and Department of Thoracic Surgery of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China. Item in Clipboard Wei Wan et al. Autophagy. 2023. Show details Display options Display options Format AbstractPubMedPMID doi: 10.1080/15548627.2023.2202108. Online…
Borrelia burgdorferi engages mammalian type I interferon responses via the cGAS-STING pathway
ABSTRACT Borrelia burgdorferi, the etiologic agent of Lyme disease, is a spirochete that modulates numerous host pathways to cause a chronic, multi-system inflammatory disease in humans. B. burgdorferi infection can lead to Lyme carditis, neurologic complications, and arthritis, due to the ability of specific borrelial strains to disseminate, invade, and…
DataSheet1_Licorice extract inhibits the cGAS-STING pathway and protects against non-alcoholic steatohepatitis.pdf
Background: Inflammation and fibrosis are typical symptoms of non-alcoholic steatohepatitis (NASH), which is one of the most common chronic liver diseases. The cGAS-STING signaling pathway has been implicated in the progression of NASH, and targeting this pathway may represent a new therapeutic strategy. Licorice is a widely used herb with…
The cGAS-STING pathway drives type I IFN immunopathology in COVID-19.
Domizio, Jeremy Di; Gulen, Muhammet F; Saidoune, Fanny; Thacker, Vivek V; Yatim, Ahmad; Sharma, Kunal; Nass, Théo; Guenova, Emmanuella; Schaller, Martin; Conrad, Curdin; Goepfert, Christine; de Leval, Laurence; Garnier, Christophe von; Berezowska, Sabina; Dubois, Anaëlle; Gilliet, Michel; Ablasser, Andrea (2022). The cGAS-STING pathway drives type I IFN immunopathology in COVID-19….
cGAS-STING properly eliminates murine norovirus an infection however antagonizes the antiviral motion regarding N-terminus of RIG-I within computer mouse macrophages.
reticulatum, H. spinifera as well as L. polyedrum, displaying anatomical as well as toxic traits; (two) Adriatic ranges associated with Alexandrium minutum, Alexandrium ostenfeldii along with Prorocentrum lima as their dangerous profiles are usually weighed against that relating to strains of various geographical sources; (iii) F. japonica and Ostreopsis cf….
Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity: Molecular Therapy
cGAS-STING signaling is a central component in the therapeutic action of most existing cancer therapies. The accumulated knowledge of tumor immunoregulatory network in recent years has spurred the development of cGAS-STING agonists for tumor treatment as an effective immunotherapeutic strategy. However, the clinical translation of these agonists is thus far…
Schisandrin C enhances cGAS-STING pathway activation and inhibits HBV replication
Ethnopharmacological relevance: Schisandra Chinensis (Turcz.) Baill. is a long-term used traditional Chinese medicine with the functions of tonifying the kidney and calming the heart, tonifying qi and engendering fluid. It can be used to treat insomnia and dreaminess, spermatorrhea, coughs, as well as liver and kidney deficiency of Yin or…
Biomaterial-enabled therapeutic modulation of cGAS-STING signaling for enhancing antitumor immunity
Review . 2023 Mar 30;S1525-0016(23)00159-4. doi: 10.1016/j.ymthe.2023.03.026. Online ahead of print. Affiliations Expand Affiliations 1 School of Life Science, Chongqing University, Chongqing 400044, P. R. China. 2 School of Life Science, Chongqing University, Chongqing 400044, P. R. China. Electronic address: luozhong918@cqu.edu.cn. Item in Clipboard Review Yingqi Liu et al. Mol Ther….
The cGAS-STING-mediated NLRP3 inflammasome is involved in the neurotoxicity induced by manganese exposure
Review doi: 10.1016/j.biopha.2022.113680. Epub 2022 Sep 7. Affiliations Expand Affiliations 1 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, Gansu, China. 2 Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, Gansu, China. Electronic address: huiwang@lzu.edu.cn. Item in Clipboard Review Jingjing Liu et al. Biomed Pharmacother. 2022 Oct….
Manganese(II) Complexes Stimulate Antitumor Immunity via Aggravating DNA Damage and Activating cGAS-STING Pathway
Activating cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a promising immunotherapeutic strategy for cancer treatment. Manganese(II) complexes MnPC and MnPVA (P = 1,10-phenanthroline, C = chlorine, VA = valproic acid) were found to activate the cGAS-STING pathway. The complexes not only damaged DNA, but also inhibited histone deacetylases…
Molecular mechanisms of mitochondrial DNA release and activation of the cGAS-STING pathway
Review doi: 10.1038/s12276-023-00965-7. Online ahead of print. Affiliations Expand Affiliations 1 Department of Biochemistry, The Catholic University of Korea College of Medicine, Seoul, 06591, South Korea. jhk@catholic.ac.kr. 2 Department of Biochemistry, The Catholic University of Korea College of Medicine, Seoul, 06591, South Korea. 3 Laboratory of Obesity and Aging Research,…
cGAS-STING pathway as a potential trigger of immunosenescence and inflammaging
Figure 1 cGAS-STING pathway. Loss of Lamin B1, increased oxidative stress, genomic instability, mitochondrial dysfunction,… Figure 1 cGAS-STING pathway. Loss of Lamin B1, increased oxidative stress, genomic instability, mitochondrial dysfunction, as well as reduced expression of nucleases, lead to dsDNA break and accumulation in cytosol. Cytoplasmic cGAS recognizes dsDNA and synthetizes…
Classifying cGAS-STING Activity Links Chromosomal Instability with Immunotherapy Response in Metastatic Bladder Cancer
The cGAS-STING pathway serves a critical role in anticancer therapy. Particularly, response to immunotherapy is likely driven by both active cGAS-STING signaling that attracts immune cells, and by the presence of cancer neoantigens that presents as targets for cytotoxic T cells. Chromosomal instability (CIN) is a hallmark of cancer, but…
NIH 2019 Discovery of cGAS Inhibitors for Interferon-Driven Autoimmune Diseases
Cytoplasmic nucleic acids alert the immune system to invading pathogens and trigger a robust type I interferon (IFN) response via activation of the STING (stimulator of interferon genes) receptor. The sensor for cytoplasmic nucleic acids was recently discovered to be cyclic GMP-AMP synthase, an enzyme that produces a unique cyclic…
Novobiocin attacks BRCA-mutated cancer cells from within and without, study shows
Efficacy of POLθ inhibition in HR-deficient cancers requires CD8+ T cells. a, b K14-Cre-Brca1f/f;Trp53f/f TNBC tumors from syngeneic FVB/129P2 mice (VEH, n = 5; NVB, n = 7) (a), or Brca2 KO KPC PDAC tumors from syngeneic C57BL/6 mice (VEH, n = 7; NVB, n = 6) (b) were subjected to IHC for CD3, CD4, and CD8 expression….
Specific activation of cGAS-STING pathway by nanotherapeutics-mediated ferroptosis evoked endogenous signaling for boosting systemic tumor immunotherapy
. 2023 Feb 23;S2095-9273(23)00131-7. doi: 10.1016/j.scib.2023.02.027. Online ahead of print. Affiliations Expand Affiliations 1 Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072, China. 2 Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan 430072,…
STING agonism turns human T cells into interferon-producing cells but impedes their functionality
. 2023 Mar 6;24(3):e55536. doi: 10.15252/embr.202255536. Epub 2023 Jan 27. Niklas Kuhl # 1 2 , Andreas Linder # 1 2 , Nora Philipp 1 3 , Daniel Nixdorf 1 3 , Hannah Fischer 1 , Simon Veth 4 , Gunnar Kuut 1 , Teng Teng Xu 1 3 , Sebastian Theurich 1 3…
Response to ‘Hyperbaric oxygen facilitates teniposide-induced cGAS-STING activation to enhance the antitumor efficacy of PD-1 antibody in HCC’ by Yang et al
. 2023 Mar;11(3):e006648. doi: 10.1136/jitc-2022-006648. Affiliations Expand Affiliations 1 Department of Hepatic Surgery and Liver Transplantation Center, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China. 2 Department of Biotherapy Center, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China. 3 Department of Hepatic Surgery and Liver Transplantation…
cGAMP-activated cGAS-STING signaling: its bacterial origins and evolutionary adaptation by metazoans
Review doi: 10.1038/s41594-023-00933-9. Online ahead of print. Affiliations Expand Affiliations 1 Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. pateld@mskcc.org. 2 Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. 3 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China. Item in Clipboard Review Dinshaw…
Chromosomal instability as central hallmark of Breast Cancer
Introduction In recent years, CIN has gained great importance due to its implications for both, the diagnosis and prognosis of cancer. Recent studies have suggested that both CIN and clonal heterogeneity, influence cancer progression, aggressiveness, prognosis, and response to therapy.1–4 The above because both, CIN and clonal heterogeneity, lead to…
STING directly recruits WIPI2 for autophagosome formation during STING-induced autophagy
The cGAS-STING pathway plays an important role in host defense by sensing pathogen DNA, inducing type I IFNs, and initiating autophagy. However, the molecular mechanism of autophagosome formation in cGAS-STING pathway-induced autophagy is still unclear. Here, we report that STING directly interacts with WIPI2, which is the key protein for…
Intercellular transmission of cGAS-STING signaling in cancer
Figure 1 Intercellular communication in cGAS-STING signaling. (A) Schematic diagram of canonical cGAS-STING signaling. The… Figure 1 Intercellular communication in cGAS-STING signaling. (A) Schematic diagram of canonical cGAS-STING signaling. The DNA sensor cyclic GMP-AMP synthase (cGAS) recognizes a wide range of double-strand DNA (dsDNA) and is activated, thus generating the…
SARS-CoV-2 infection activates the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway in the lung: a review
Keywords SARS-CoV-2, COVID-19, cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway, lung damage, interferon, cytokines Introduction Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) pandemic with origin in Wuhan, China [1]. With confirmed 522 million infections and death of 6.27 million until May…
Viruses | Free Full-Text | Manganese Mediates Its Antiviral Functions in a cGAS-STING Pathway Independent Manner
Received: 4 February 2023 / Revised: 25 February 2023 / Accepted: 27 February 2023 / Published: 28 February 2023 Round 1 Reviewer 1 Report Authors demonstrated that Mn2+ exhibits antiviral effects and inhibits RNA and DNA viruses replications in a cGAS-STING independent manner. Their results reveal that Mn2+ may harbor…
STAT6 Rabbit mAb | cGAS-STING Signaling | Antibodies | Products
Usage: hover your mouse-pointer anywhere on the image above to see an enlarged portion of the image. You can also just click the image to see the original-sized version. Description: STAT6 is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family…
Crosstalk between cGAS-STING pathway and autophagy in cancer immunity
1 Introduction Cancer is one of the world’s most serious threats to human health, with high morbidity and mortality rates, and according to the latest global data, 9.96 million patients will die from cancer in 2020 (1). Cancer is a genetic abnormal disease triggered by a long-term combination of multiple…
Grouper cGAS is a negative regulator of STING-mediated interferon response
doi: 10.3389/fimmu.2023.1092824. eCollection 2023. Luhao Zhang 1 , Xin Zhang 1 , Jiaming Liao 1 , Linting Xu 1 , Shaozhu Kang 1 , Hong Chen 1 , Mengshi Sun 1 , Siting Wu 1 , Zhuqing Xu 1 , Shina Wei 1 2 , Qiwei Qin 1 3 4 5 , Jingguang Wei 1 6…
Mitochondrial DNA in cell death and inflammation | Biochemical Society Transactions
Apoptosis is divided into extrinsic and intrinsic apoptotic cell death depending on the origin of cell death ligand. Activation of apoptosis from the cell exterior — extrinsic apoptosis — is induced upon binding of cognate ligands to death receptors [4–7], as well as the assembly of intracellular death complexes such…
Pharmacological inhibition of the cGAS-STING signaling pathway suppresses microglial M1-polarization in the spinal cord and attenuates neuropathic pain(BMU101-EN-5.273)
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The role of chemerin in the regulation of cGAS-STING pathway in gestational diabetes mellitus placenta
Recent studies already confirmed that placenta mitochondrial dysfunction is associated with the progression of gestational diabetes mellitus (GDM). Besides, a possible relationship between adipokine chemerin and disulfide-bond A oxidoreductase-like protein (DsbA-L) had been revealed, whereas the potential interaction remains unclear. In addition, very little is still known about the cyclic…
African Swine Fever Virus L83L Negatively Regulates the cGAS-STING-Mediated IFN-I Pathway by Recruiting Tollip To Promote STING Autophagic Degradation
African swine fever (ASF) is a devastating infectious disease of pigs caused by the African swine fever virus (ASFV), which poses a great danger to the global pig industry. Many viral proteins can suppress with interferon signaling to evade the host’s innate immune responses. Therefore, the development of an effective…
Leaked genomic and mitochondrial DNA contribute to the host response to noroviruses in a STING-dependent manner
Citation Jahun, A. S., Sorgeloos, F., Chaudhry, Y., Arthur, S. E., Hosmillo, M., Georgana, I., Izuagbe, R., & et al. Leaked genomic and mitochondrial DNA contribute to the host response to noroviruses in a STING-dependent manner. Cell Reports doi.org/10.17863/CAM.93870 Abstract The cGAS-STING pathway is central to the interferon response against…
Association of circulating MtDNA with CVD in hemodialysis patients and in vitro effect of exogenous MtDNA on cardiac microvascular inflammation | BMC Cardiovascular Disorders
Thompson S, James M, Wiebe N, Hemmelgarn B, Manns B, Klarenbach S, Tonelli M. Cause of death in patients with Reduced Kidney Function. J Am Soc Nephrol. 2015;26(10):2504–11. Article Google Scholar Matsushita K, Coresh J, Sang Y, Chalmers J, Fox C, Guallar E, Jafar T, Jassal SK, Landman GW, Muntner…
Viruses that Cause Cancer Recruit Human Protein to Evade Immune Response
Credit: xfzsy/Getty Images Viruses have evolved with humans for millions of years, so it’s no surprise they’ve evolved tricks to evade our natural, or innate, immune responses. Unfortunately, it’s often unclear what these tricks are. But now, thanks to researchers at the University of North Carolina (UNC) School of Medicine,…
A path towards personalized medicine for autoinflammatory and related diseases
The human stories behind rare rheumatic diseases illustrate how genetic information can benefit patients. In 1988, a team of physicians met a patient with a unique disease of multiple organs, including the kidneys, liver, brain and eyes7. No immunosuppressive therapy was effective, and the patient and several of his family…
Manganese Mediates its Antiviral Functions in a cGAS-STING Pathway Independent Manner[v1]
Preprint Article Version 1 This version is not peer-reviewed , , , , , , , , , , * , * Sun, S.; Xu, X.; Qiu, M.; Jiang, S.; Cao, Q.; Luo, J.; Zhang, T.; Chen, N.; Zheng, W.; Meurens, F.; Liu, Z.; Zhu, J. Manganese Mediates its Antiviral…
EV-A71, CA16, and EMCV 2C proteins antagonized cGAS-STING signaling pathway activation by impairing the interaction between STING and TBK1.
(A) HEK-293T cells were transfected with 1 μg of empty vector or the indicated FLAG-2C-expressing plasmids, along with 1 μg of empty vector or HA-cGAS plus HA-STING expressing plasmids. At 24 hpt, the IFN-β protein amount in the supernatant was determined by ELISA, and the expression of 2C was confirmed…
Innate sensing of picornavirus infection involves cGAS-STING-mediated antiviral responses triggered by mitochondrial DNA release
Cyclic GMP-AMP synthase (cGAS) plays a key role in the innate immune responses to both DNA and RNA virus infection. Here, we found that enterovirus 71 (EV-A71), Seneca Valley virus (SVV), and foot-and-mouth disease virus (FMDV) infection triggered mitochondria damage and mitochondrial DNA (mtDNA) release in vitro and vivo. These…
Melatonin Suppresses Cyclic GMP-AMP Synthase-Stimulator of Interferon Genes Signaling and Delays the Development of Hearing Loss in the C57BL/6J Presbycusis Mouse Model
Melatonin supplementation has been shown to delay age-related hearing loss (ARHL) progression. Previously, melatonin was found to inhibit neuronal mitochondrial DNA (mtDNA) release, as well as inhibit cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling, thereby delaying the onset of central nervous system diseases. Therefore, we hypothesized that melatonin…
Activation of the NLRP1 inflammasome in human keratinocytes by the dsDNA mimetic poly(dA:dT)
The accrual of cytosolic DNA leads to transcription of type I IFNs, proteolytic maturation of the IL-1 family of cytokines, and pyroptotic cell death. Caspase-1 cleaves pro-IL1β to generate mature bioactive cytokine and gasdermin D which facilitates IL-1 release and pyroptotic cell death. Absent in melanoma-2 (AIM2) is a sensor…
Cytosolic DNA sensing by cGAS/STING promotes TRPV2-mediated Ca2+ release to protect stressed replication forks: Molecular Cell
Causes and consequences of replication stress. Nat. Cell Biol. 2014; 16: 2-9doi.org/10.1038/ncb2897 Tomasetti C. Li L. Vogelstein B. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science. 2017; 355: 1330-1334doi.org/10.1126/science.aaf9011 Endogenous DNA damage as a source of genomic instability in cancer. Cell. 2017; 168: 644-656doi.org/10.1016/j.cell.2017.01.002 Halazonetis T.D. Gorgoulis…
Role of STING protein in breast cancer: mechanisms and therapeutic implications
Review doi: 10.1007/s12032-022-01908-4. Affiliations Expand Affiliations 1 Department of Vascular and Endocrine Surgery, Xijing Hospital, The Air Force Medical University, Xi’an, 710000, China. 2 Department of Vascular and Endocrine Surgery, Xijing Hospital, The Air Force Medical University, Xi’an, 710000, China. vascularzhang@outlook.com. Item in Clipboard Review Yue Jiang et al. Med Oncol….
Emerging role of STING signalling in CNS injury: inflammation, autophagy, necroptosis, ferroptosis and pyroptosis | Journal of Neuroinflammation
Langlois JA, Rutland-Brown W, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil. 2006;21:375–8. doi.org/10.1097/00001199-200609000-00001. Article PubMed Google Scholar Cao HQ, Dong ED. An update on spinal cord injury research. Neurosci Bull. 2013;29:94–102. doi.org/10.1007/s12264-012-1277-8. Article PubMed Google Scholar O’Donnell MJ, Xavier D,…
Figure 2 | Identification of Cytosolic DNA Sensor cGAS-STING as Immune-Related Risk Factor in Renal Carcinoma following Pan-Cancer Analysis
Expression landscape of the cGAS-STING sensor across human cancers. (a) The expression score of the cGAS-STING signal in paired tumor and nontumor tissues. (b) Significant difference of the cGAS-STING score between tumor and normal samples. BLCA: bladder urothelial carcinoma; BRCA: breast invasive carcinoma; CESC: cervical squamous cell carcinoma and endocervical…
Hydrogen Sulfide Ameliorated High Choline-Induced Cardiac Dysfunction by Inhibiting cGAS-STING-NLRP3 Inflammasome Pathway
Although it is an essential nutrient, high choline intake directly or indirectly via its metabolite is associated with increased risk of cardiovascular disease, the mechanism of which remains to be elucidated. The present study was performed to investigate whether hydrogen sulfide (H2S) was involved in high choline-induced cardiac dysfunction and…
Maintaining manganese in tumor to activate cGAS-STING pathway evokes a robust abscopal anti-tumor effect.
Affiliation Wang C(1), Sun Z(1), Zhao C(1), Zhang Z(1), Wang H(1), Liu Y(1), Guo Y(1), Zhang B(1), Gu L(2), Yu Y(2), Hu Y(3), Wu J(4).Author information: (1)State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, School of Life Sciences, Nanjing University, Nanjing 210093, PR China. (2)State…
First-of-its-kind platform generates antitumor immunity and improves responses to checkpoint inhibitors
Researchers at The University of Texas MD Anderson Cancer Center have developed an ultrasound-guided cancer immunotherapy platform that generates systemic antitumor immunity and improves the therapeutic efficacy of immune checkpoint blockade. The findings from the preclinical study were published today in Nature Nanotechnology. As the first-of-its-kind platform, the Microbubble-assisted UltraSound-guided…
How a genetic mutation affects the body’s immune system response to viruses, development of blood cancers
Graphical abstract. Credit: Cell Reports (2022). DOI: 10.1016/j.celrep.2022.110856 The body’s innate immune system, active from birth, is the first line of defense against viruses and other pathogens that cause disease. Using vaccination as an example, after receiving a vaccine, pain, redness, or swelling may occur at the injection site. This…
By keeping the Immune System in good condition, Gut Microbiome protects us from viral infections
The gut microbiota is crucial for health. However, how these non-invasive microbes communicate with the rest of the body to improve host physiology is not fully understood. Researchers from Stockholm, Umea, and Gothenburg Universities, Sweden, claim that the gut microbiota is essential for natural resistance to viral infections. This evidence…
A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis
This article was originally published here Nat Cell Biol. 2022 May 2. doi: 10.1038/s41556-022-00894-z. Online ahead of print. ABSTRACT Innate DNA sensing via the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) mechanism surveys microbial invasion and cellular damage and thus participates in various human infectious diseases, autoimmune diseases and cancers….
Circulating cell-free mtDNA release is associated with the activation of cGAS-STING pathway and inflammation in mitochondrial diseases
Craven L, Alston C, Taylor R, Turnbull D (2017) Recent advances in mitochondrial disease. Annu Rev Genomics Hum Genet 18:257–275. doi.org/10.1146/annurev-genom-091416-035426 CAS Article PubMed Google Scholar El-Hattab AW, Adesina AM, Jones J, Scaglia F (2015) MELAS syndrome: clinical manifestations, pathogenesis, and treatment options. Mol Genet Metab 116(1–2):4–12. doi.org/10.1016/j.ymgme.2015.06.004 CAS Article …
Role of cGAS-STING in SARS-CoV-2 infection
Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that led to the coronavirus disease 2019 (COVID-19) pandemic can cause various clinical presentations ranging from asymptomatic and mild disease to critical and even deadly outcomes. The pathogenesis of COVID-19 is directly associated with the destruction of lung epithelial cells,…
Activation of STING by targeting a pocket in the transmembrane domain
Zhang, X., Bai, XC & Chen, ZJ Structures and mechanisms of the cGAS-STING innate immunity pathway. Immunity 5343–53 (2020). CAS PubMed Google Scholar Article Ishikawa, H. & Barber, GN STING is an endoplasmic reticulum adapter that facilitates innate immune signaling. Nature 455674–678 (2008). ADS CAS PubMed PubMed Central Article Google…
Inhibition of cGAS-STING by JQ1 alleviates oxidative stress-induced retina inflammation and degeneration
Atrophic (“dry”) form of age-related macular degeneration (AMD) is a leading cause of vision loss characterized by macular retinal pigment epithelium (RPE) and the ensuing photoreceptor degeneration. cGAS-STING signaling is a key cytosolic DNA sensor system in innate immunity and have recently been shown promotes RPE degeneration. However, expression regulation…
Wuhan University Song Zhiyin and other teams discovered a new mechanism of mitochondrial DNA release
Sam50 is a key component of the sorting and assembly machinery (SAM) complex and is also involved in bridging mitochondrial outer and inner membrane contacts. However, the physiological and pathological functions of Sam50 remain largely unknown. On March 21, 2022, Wuhan University Song Zhiyin and Meng Qingtao jointly published a…
Type I Interferon Response Is Mediated by NLRX1-cGAS-STING Signaling in Brain Injury
doi: 10.3389/fnmol.2022.852243. eCollection 2022. Lauren E Fritsch 1 , Jing Ju 2 , Erwin Kristobal Gudenschwager Basso 3 , Eman Soliman 3 , Swagatika Paul 4 , Jiang Chen 2 , Alexandra M Kaloss 3 , Elizabeth A Kowalski 3 , Taylor C Tuhy 5 , Rachana Deven Somaiya 1 , Xia Wang 3 , Irving Coy Allen 3 , Michelle H…
Enhanced cGAS-STING-dependent interferon signaling associated with mutations in ATAD3A
dc.identifier.citation Lepelley , A , Della Mina , E , Van Nieuwenhove , E , Waumans , L , Fraitag , S , Rice , G I , Dhir , A , Fremond , M-L , Rodero , M P , Seabra , L , Carter , E , Bodemer…