CBASS to cGAS-STING: The Origins and Mechanisms of Nucleotide Second Messenger Immune Signaling

Bacteriophages inhibit and evade cGAS-like immune function in bacteria

(2023) Erin Huiting et al.   CELL

Ubiquitin-like conjugation by bacterial cGAS enhances anti-phage defence

(2023) Justin M. Jenson et al.   NATURE

An E1–E2 fusion protein primes antiviral immune signalling in bacteria

(2023) Hannah E. Ledvina et al.   NATURE

Csx28 is a membrane pore that enhances CRISPR-Cas13b–dependent antiphage defense

(2023) Arica R. VanderWal et al.   SCIENCE

CBASS phage defense and evolution of antiviral nucleotide signaling

(2022) Brianna Duncan-Lowey et al.   CURRENT OPINION IN IMMUNOLOGY

Bacterial gasdermins reveal an ancient mechanism of cell death

(2022) Alex G. Johnson et al.   SCIENCE

Crystal structure and functional implication of bacterial STING

(2022) Tzu-Ping Ko et al.   Nature Communications

Toxin-Antitoxin Systems as Phage Defense Elements

(2022) Michele LeRoux et al.   Annual Review of Microbiology

The gut microbiota prime systemic antiviral immunity via the cGAS-STING-IFN-I axis

(2022) Saskia F. Erttmann et al.   IMMUNITY

Phage anti-CBASS and anti-Pycsar nucleases subvert bacterial immunity

(2022) Samuel J. Hobbs et al.   NATURE

Control of bacterial immune signaling by a WYL domain transcription factor

(2022) Chelsea L Blankenchip et al.   NUCLEIC ACIDS RESEARCH

ENPP1’s regulation of extracellular cGAMP is a ubiquitous mechanism of attenuating STING signaling

(2022) Jacqueline A. Carozza et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Systematic and quantitative view of the antiviral arsenal of prokaryotes

(2022) Florian Tesson et al.   Nature Communications

Cyclic nucleotide-induced helical structure activates a TIR immune effector

(2022) Gaëlle Hogrel et al.   NATURE

Cryo-EM structure of an active bacterial TIR–STING filament complex

(2022) Benjamin R. Morehouse et al.   NATURE

Prokaryotic innate immunity through pattern recognition of conserved viral proteins

(2022) Linyi Alex Gao et al.   SCIENCE

An expanded arsenal of immune systems that protect bacteria from phages

(2022) Adi Millman et al.   Cell Host & Microbe

ABCC1 transporter exports the immunostimulatory cyclic dinucleotide cGAMP

(2022) Joanna H. Maltbaek et al.   IMMUNITY

Viruses inhibit TIR gcADPR signalling to overcome bacterial defence

(2022) Azita Leavitt et al.   NATURE

Clathrin-associated AP-1 controls termination of STING signalling

(2022) Ying Liu et al.   NATURE

Ku proteins promote DNA binding and condensation of cyclic GMP-AMP synthase

(2022) Xinyue Tao et al.   Cell Reports

Multiple phage resistance systems inhibit infection via SIR2-dependent NAD+ depletion

(2022) Jeremy Garb et al.   Nature Microbiology

Type III CRISPR-Cas provides resistance against nucleus-forming jumbo phages via abortive infection

(2022) David Mayo-Muñoz et al.   MOLECULAR CELL

Direct activation of a bacterial innate immune system by a viral capsid protein

(2022) Tong Zhang et al.   NATURE

Antiviral signalling by a cyclic nucleotide activated CRISPR protease

(2022) Christophe Rouillon et al.   NATURE

Structural basis for the inactivation of cytosolic DNA sensing by the vaccinia virus

(2022) Angel Rivera-Calzada et al.   Nature Communications

The Evolution of STING Signaling and Its Involvement in Cancer

(2021) Nimi Vashi et al.   TRENDS IN BIOCHEMICAL SCIENCES

cGAS phase separation inhibits TREX1-mediated DNA degradation and enhances cytosolic DNA sensing

(2021) Wen Zhou et al.   MOLECULAR CELL

Phosphorylation and chromatin tethering prevent cGAS activation during mitosis

(2021) Tuo Li et al.   SCIENCE

Viral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion

(2021) Guangjun Xu et al.   MOLECULAR CELL

Crystal structure and functional implication of a bacterial cyclic AMP–AMP–GMP synthetase

(2021) Tzu-Ping Ko et al.   NUCLEIC ACIDS RESEARCH

Poxvirus cGAMP nucleases: Clues and mysteries from a stolen gene

(2021) Carlos Maluquer de Motes   PLoS Pathogens

Induced phase separation of mutant NF2 imprisons the cGAS-STING machinery to abrogate antitumor immunity

(2021) Fansen Meng et al.   MOLECULAR CELL

Tonic prime-boost of STING signalling mediates Niemann–Pick disease type C

(2021) Ting-Ting Chu et al.   NATURE

cGAS-like receptors sense RNA and control 3′2′-cGAMP signalling in Drosophila

(2021) Kailey M. Slavik et al.   NATURE

Two cGAS-like receptors induce antiviral immunity in Drosophila

(2021) Andreas Holleufer et al.   NATURE

Cooperative DNA binding mediated by KicGAS/ORF52 oligomerization allows inhibition of DNA-induced phase separation and activation of cGAS

(2021) Debipreeta Bhowmik et al.   NUCLEIC ACIDS RESEARCH

Molecular basis of CD-NTase nucleotide selection in CBASS anti-phage defense

(2021) Apurva A. Govande et al.   Cell Reports

Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment

(2021) Khiem C. Lam et al.   CELL

Cyclic CMP and cyclic UMP mediate bacterial immunity against phages

(2021) Nitzan Tal et al.   CELL

No Longer A One-Trick Pony: STING Signaling Activity Beyond Interferon

(2021) Jianjun Wu et al.   JOURNAL OF MOLECULAR BIOLOGY

Effector-mediated membrane disruption controls cell death in CBASS antiphage defense

(2021) Brianna Duncan-Lowey et al.   MOLECULAR CELL

Antiviral activity of bacterial TIR domains via immune signalling molecules

(2021) Gal Ofir et al.   NATURE

Specificity and sensitivity of an RNA targeting type III CRISPR complex coupled with a NucC endonuclease effector

(2021) Sabine Grüschow et al.   NUCLEIC ACIDS RESEARCH

The cyclic dinucleotide 2′3′-cGAMP induces a broad antibacterial and antiviral response in the sea anemone Nematostella vectensis

(2021) Shally R. Margolis et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Molecular mechanisms of the CdnG-Cap5 antiphage defense system employing 3′,2′-cGAMP as the second messenger

(2021) Shirin Fatma et al.   Nature Communications

Orally acquired cyclic dinucleotides drive dSTING-dependent antiviral immunity in enterocytes

(2021) Elisha Segrist et al.   Cell Reports

STING mediates immune responses in the closest living relatives of animals

(2021) Arielle Woznica et al.   eLife

Structure and Mechanism of a Cyclic Trinucleotide-Activated Bacterial Endonuclease Mediating Bacteriophage Immunity

(2020) Rebecca K. Lau et al.   MOLECULAR CELL

HORMA Domain Proteins and a Trip13-like ATPase Regulate Bacterial cGAS-like Enzymes to Mediate Bacteriophage Immunity

(2020) Qiaozhen Ye et al.   MOLECULAR CELL

The arms race between bacteria and their phage foes

(2020) Hannah G. Hampton et al.   NATURE

PCBP1 modulates the innate immune response by facilitating the binding of cGAS to DNA

(2020) Chen-Yang Liao et al.   Cellular & Molecular Immunology

CBASS Immunity Uses CARF-Related Effectors to Sense 3′–5′- and 2′–5′-Linked Cyclic Oligonucleotide Signals and Protect Bacteria from Phage Infection

(2020) Brianna Lowey et al.   CELL

Intercepting second-messenger signaling by rationally designed peptides sequestering c-di-GMP

(2020) Chee-Seng Hee et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Abortive Infection: Bacterial Suicide as an Antiviral Immune Strategy

(2020) Anna Lopatina et al.   Annual Review of Virology

Structural basis for nucleosome-mediated inhibition of cGAS activity

(2020) Duanfang Cao et al.   CELL RESEARCH

Conserved strategies for pathogen evasion of cGAS–STING immunity

(2020) James B Eaglesham et al.   CURRENT OPINION IN IMMUNOLOGY

STING cyclic dinucleotide sensing originated in bacteria

(2020) Benjamin R. Morehouse et al.   NATURE

The Molecular Basis of Tight Nuclear Tethering and Inactivation of cGAS

(2020) Baoyu Zhao et al.   NATURE

Prokaryotic viperins produce diverse antiviral molecules

(2020) Aude Bernheim et al.   NATURE

Structural basis for sequestration and autoinhibition of cGAS by chromatin

(2020) Sebastian Michalski et al.   NATURE

Structural mechanism of cGAS inhibition by the nucleosome

(2020) Ganesh R. Pathare et al.   NATURE

BAF restricts cGAS on nuclear DNA to prevent innate immune activation

(2020) Baptiste Guey et al.   SCIENCE

Diverse enzymatic activities mediate antiviral immunity in prokaryotes

(2020) Linyi Gao et al.   SCIENCE

Structural basis for the inhibition of cGAS by nucleosomes

(2020) Tomoya Kujirai et al.   SCIENCE

Structural basis of nucleosome-dependent cGAS inhibition

(2020) Joshua A. Boyer et al.   SCIENCE

Diversity and classification of cyclic-oligonucleotide-based anti-phage signalling systems

(2020) Adi Millman et al.   Nature Microbiology

Viral cGAMP nuclease reveals the essential role of DNA sensing in protection against acute lethal virus infection

(2020) Bruno Hernáez et al.   Science Advances

2′3′-cGAMP triggers a STING- and NF-κB–dependent broad antiviral response in Drosophila

(2020) Hua Cai et al.   Science Signaling

Structures of diverse poxin cGAMP nucleases reveal a widespread role for cGAS-STING evasion in host–pathogen conflict

(2020) James B Eaglesham et al.   eLife

cGAS in action: Expanding roles in immunity and inflammation

(2019) Andrea Ablasser et al.   SCIENCE

Bacterial cGAS-like enzymes synthesize diverse nucleotide signals

(2019) Aaron T. Whiteley et al.   NATURE

Structural basis of STING binding with and phosphorylation by TBK1

(2019) Conggang Zhang et al.   NATURE

Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP–AMP

(2019) Guijun Shang et al.   NATURE

Autophagy induction via STING trafficking is a primordial function of the cGAS pathway

(2019) Xiang Gui et al.   NATURE

Viral and metazoan poxins are cGAMP-specific nucleases that restrict cGAS–STING signalling

(2019) James B. Eaglesham et al.   NATURE

Acetylation Blocks cGAS Activity and Inhibits Self-DNA-Induced Autoimmunity

(2019) Jiang Dai et al.   CELL

SLC19A1 Is an Importer of the Immunotransmitter cGAMP

(2019) Christopher Ritchie et al.   MOLECULAR CELL

A conserved PLPLRT/SD motif of STING mediates the recruitment and activation of TBK1

(2019) Baoyu Zhao et al.   NATURE

Human cGAS catalytic domain has an additional DNA-binding interface that enhances enzymatic activity and liquid-phase condensation

(2019) Wei Xie et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Modular Architecture of the STING C-Terminal Tail Allows Interferon and NF-κB Signaling Adaptation

(2019) Carina C. de Oliveira Mann et al.   Cell Reports

Interferon-Stimulated Genes: What Do They All Do?

(2019) John W. Schoggins   Annual Review of Virology

Cyclic GMP–AMP signalling protects bacteria against viral infection

(2019) Daniel Cohen et al.   NATURE

SLC19A1 transports immunoreactive cyclic dinucleotides

(2019) Rutger D. Luteijn et al.   NATURE

NAD+ cleavage activity by animal and plant TIR domains in cell death pathways

(2019) Shane Horsefield et al.   SCIENCE

The pan-immune system of bacteria: antiviral defence as a community resource

(2019) Aude Bernheim et al.   NATURE REVIEWS MICROBIOLOGY

cGAS and CD-NTase enzymes: structure, mechanism, and evolution

(2019) Philip J Kranzusch   CURRENT OPINION IN STRUCTURAL BIOLOGY

Structure of the Human cGAS–DNA Complex Reveals Enhanced Control of Immune Surveillance

(2018) Wen Zhou et al.   CELL

Inflammation-Induced, STING-Dependent Autophagy Restricts Zika Virus Infection in the Drosophila Brain

(2018) Yuan Liu et al.   Cell Host & Microbe

TIR Domain Proteins Are an Ancient Family of NAD + -Consuming Enzymes

(2018) Kow Essuman et al.   CURRENT BIOLOGY

Direct activation of a phospholipase by cyclic GMP-AMP in El TorVibrio cholerae

(2018) Geoffrey B. Severin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

DNA-induced liquid phase condensation of cGAS activates innate immune signaling

(2018) Mingjian Du et al.   SCIENCE

Systematic discovery of antiphage defense systems in the microbial pangenome

(2018) Shany Doron et al.   SCIENCE

TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA sensing

(2018) Gil Ju Seo et al.   Nature Communications

Analysis of Drosophila STING Reveals an Evolutionarily Conserved Antimicrobial Function

(2018) Marina Martin et al.   Cell Reports

The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila

(2018) Akira Goto et al.   IMMUNITY

ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response

(2018) Huan Lian et al.   Nature Communications

Tumor-Derived cGAMP Triggers a STING-Mediated Interferon Response in Non-tumor Cells to Activate the NK Cell Response

(2018) Assaf Marcus et al.   IMMUNITY

DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing

(2018) Simon R. Scutts et al.   Cell Reports

Sensing of Bacterial Cyclic Dinucleotides by the Oxidoreductase RECON Promotes NF-κB Activation and Shapes a Proinflammatory Antibacterial State

(2017) Adelle P. McFarland et al.   IMMUNITY

Type III CRISPR–Cas systems produce cyclic oligoadenylate second messengers

(2017) Ole Niewoehner et al.   NATURE

cGAS senses long and HMGB/TFAM-bound U-turn DNA by forming protein–DNA ladders

(2017) Liudmila Andreeva et al.   NATURE

A cyclic oligonucleotide signaling pathway in type III CRISPR-Cas systems

(2017) Migle Kazlauskiene et al.   SCIENCE

Sumoylation Promotes the Stability of the DNA Sensor cGAS and the Adaptor STING to Regulate the Kinetics of Response to DNA Virus

(2016) Ming-Ming Hu et al.   IMMUNITY

iRhom2 is essential for innate immunity to DNA viruses by mediating trafficking and stability of the adaptor STING

(2016) Wei-Wei Luo et al.   NATURE IMMUNOLOGY

Glutamylation of the DNA sensor cGAS regulates its binding and synthase activity in antiviral immunity

(2016) Pengyan Xia et al.   NATURE IMMUNOLOGY

Structural basis for concerted recruitment and activation of IRF-3 by innate immune adaptor proteins

(2016) Baoyu Zhao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein MAB21L1

(2016) Carina C. de Oliveira Mann et al.   Scientific Reports

A Novel Oculo-Skeletal syndrome with intellectual disability caused by a particular MAB21L2 mutation

(2015) Denise Horn et al.   European Journal of Medical Genetics

Cutting Edge: cGAS Is Required for Lethal Autoimmune Disease in the Trex1-Deficient Mouse Model of Aicardi–Goutières Syndrome

(2015) Elizabeth E. Gray et al.   JOURNAL OF IMMUNOLOGY

Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2′,3′ cGAMP Signaling

(2015) Philip J. Kranzusch et al.   MOLECULAR CELL

A bacterial cyclic dinucleotide activates the cytosolic surveillance pathway and mediates innate resistance to tuberculosis

(2015) Bappaditya Dey et al.   NATURE MEDICINE

Comparative genomic analyses reveal a vast, novel network of nucleotide-centric systems in biological conflicts, immunity and signaling

(2015) A. Maxwell Burroughs et al.   NUCLEIC ACIDS RESEARCH

Endosymbiotic theories for eukaryote origin

(2015) William F. Martin et al.   PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES

Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases

(2015) Daxing Gao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Viruses transfer the antiviral second messenger cGAMP between cells

(2015) A. Bridgeman et al.   SCIENCE

Transmission of innate immune signaling by packaging of cGAMP in viral particles

(2015) Matteo Gentili et al.   SCIENCE

Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation

(2015) S. Liu et al.   SCIENCE

Structure-Guided Reprogramming of Human cGAS Dinucleotide Linkage Specificity

(2014) Philip J. Kranzusch et al.   CELL

Structural Biochemistry of a Vibrio cholerae Dinucleotide Cyclase Reveals Cyclase Activity Regulation by Folates

(2014) Deyu Zhu et al.   MOLECULAR CELL

Transferred interbacterial antagonism genes augment eukaryotic innate immune function

(2014) Seemay Chou et al.   NATURE

Hydrolysis of 2′3′-cGAMP by ENPP1 and design of nonhydrolyzable analogs

(2014) Lingyin Li et al.   Nature Chemical Biology

Molecular evolutionary and structural analysis of the cytosolic DNA sensor cGAS and STING

(2014) Xiaomei Wu et al.   NUCLEIC ACIDS RESEARCH

The Cytosolic DNA Sensor cGAS Forms an Oligomeric Complex with DNA and Undergoes Switch-like Conformational Changes in the Activation Loop

(2014) Xu Zhang et al.   Cell Reports

Structure-Function Analysis of STING Activation by c[G(2′,5′)pA(3′,5′)p] and Targeting by Antiviral DMXAA

(2013) Pu Gao et al.   CELL

Cyclic [G(2′,5′)pA(3′,5′)p] Is the Metazoan Second Messenger Produced by DNA-Activated Cyclic GMP-AMP Synthase

(2013) Pu Gao et al.   CELL

Cyclic GMP-AMP Synthase Is Activated by Double-Stranded DNA-Induced Oligomerization

(2013) Xin Li et al.   IMMUNITY

Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High-Affinity Ligand for STING

(2013) Xu Zhang et al.   MOLECULAR CELL

cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING

(2013) Andrea Ablasser et al.   NATURE

Structural mechanism of cytosolic DNA sensing by cGAS

(2013) Filiz Civril et al.   NATURE

Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP

(2013) Andrea Ablasser et al.   NATURE

Structure of Human cGAS Reveals a Conserved Family of Second-Messenger Enzymes in Innate Immunity

(2013) Philip J. Kranzusch et al.   Cell Reports

The Innate Immune DNA Sensor cGAS Produces a Noncanonical Cyclic Dinucleotide that Activates Human STING

(2013) Elie J. Diner et al.   Cell Reports

A Mechanism for the Inhibition of DNA-PK-Mediated DNA Sensing by a Virus

(2013) Nicholas E. Peters et al.   PLoS Pathogens

Coordinated Regulation of Accessory Genetic Elements Produces Cyclic Di-Nucleotides for V. cholerae Virulence

(2012) Bryan W. Davies et al.   CELL

Structural Analysis of the STING Adaptor Protein Reveals a Hydrophobic Dimer Interface and Mode of Cyclic di-GMP Binding

(2012) Songying Ouyang et al.   IMMUNITY

The structural basis for the sensing and binding of cyclic di-GMP by STING

(2012) Yi-He Huang et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway

(2012) L. Sun et al.   SCIENCE

Activation of STAT6 by STING Is Critical for Antiviral Innate Immunity

(2011) Huihui Chen et al.   CELL

NF-κB in immunobiology

(2011) Matthew S Hayden et al.   CELL RESEARCH

Defense Islands in Bacterial and Archaeal Genomes and Prediction of Novel Defense Systems

(2011) K. S. Makarova et al.   JOURNAL OF BACTERIOLOGY

STING is a direct innate immune sensor of cyclic di-GMP

(2011) Dara L. Burdette et al.   NATURE

Horizontal gene transfer between bacteria and animals

(2011) Julie C. Dunning Hotopp   TRENDS IN GENETICS

The Oligoadenylate Synthetase Family: An Ancient Protein Family with Multiple Antiviral Activities

(2010) Helle Kristiansen et al.   JOURNAL OF INTERFERON AND CYTOKINE RESEARCH

c-di-AMP Secreted by Intracellular Listeria monocytogenes Activates a Host Type I Interferon Response

(2010) J. J. Woodward et al.   SCIENCE

A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP

(2009) Sarah M. McWhirter et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Origin and evolution of the adaptive immune system: genetic events and selective pressures

(2009) Martin F. Flajnik et al.   NATURE REVIEWS GENETICS

The Adaptor Protein MITA Links Virus-Sensing Receptors to IRF3 Transcription Factor Activation

(2008) Bo Zhong et al.   IMMUNITY

STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling

(2008) Hiroki Ishikawa et al.   NATURE