Affinage

STING1

Stimulator of interferon genes protein · UniProt Q86WV6

Round 2 corrected
Length
379 aa
Mass
42.2 kDa
Annotated
2026-04-28
130 papers in source corpus 46 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STING1 is a central innate immune adaptor and direct cyclic dinucleotide receptor that couples cytosolic DNA sensing to type I interferon induction, NF-κB activation, autophagy, and lysosomal biogenesis. Residing on the ER membrane as an autoinhibited dimer, STING binds 2'3'-cGAMP produced by cGAS, undergoes a 180° ligand-binding domain rotation that drives disulfide-linked polymerization via Cys148, palmitoylation at Cys88/91 at the Golgi, and oligomerization-dependent recruitment of TBK1—whose C-terminal tail interaction and trans-phosphorylation of STING Ser366 enables IRF3 recruitment and phosphorylation (PMID:18724357, PMID:25636800, PMID:30842659, PMID:31230712, PMID:27324217, PMID:30842653). STING trafficking from ER to ERGIC/Golgi is regulated by TAK1-mediated Ser355 phosphorylation, microtubule interactions, RNF144A-catalyzed K6-ubiquitination, and lipid peroxidation-dependent carbonylation at C88, while signal termination involves ULK1 phosphorylation, UXT/SQSTM1-mediated autophagic degradation, and C9orf72-dependent lysosomal turnover (PMID:24119841, PMID:37832545, PMID:36857187, PMID:32541831, PMID:32814898, PMID:35543189). Beyond canonical interferon signaling, STING drives TBK1-independent noncanonical autophagy through WIPI2-dependent LC3 lipidation at ERGIC membranes, GABARAP-mediated TFEB activation for lysosomal biogenesis, LRRK2 kinase activation, and nuclear translocation to activate AHR-dependent transcription for gut homeostasis—with gain-of-function mutations causing STING-associated vasculopathy with onset in infancy (SAVI) (PMID:30842662, PMID:39423796, PMID:39812709, PMID:38016467, PMID:25029335).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2008 High

    The identification of STING as an ER-resident transmembrane adaptor that activates IRF3 and NF-κB upon cytosolic DNA or viral challenge established the missing link between cytoplasmic nucleic acid detection and type I interferon induction.

    Evidence Two independent expression-cloning screens with RNAi knockdown, co-IP, and subcellular fractionation in human cells

    PMID:18724357 PMID:18818105

    Open questions at the time
    • Initial reports disagreed on ER versus mitochondrial localization
    • Upstream sensor identity (cGAS) was unknown
    • Mechanism of STING activation was undefined
  2. 2009 High

    Demonstration that forced STING dimerization is sufficient for IFN induction established that oligomeric state change, rather than ligand binding per se, is the proximal activation event.

    Evidence Chemically induced dimerization with coumermycin in live-cell imaging and functional IFN assays

    PMID:19433799

    Open questions at the time
    • The endogenous ligand triggering dimerization was unknown
    • Structure of the dimer was unresolved
  3. 2011 High

    Direct binding of cyclic di-GMP to STING demonstrated that STING functions not only as a signaling adaptor but also as a bona fide innate immune receptor for cyclic dinucleotides.

    Evidence Radioligand binding assays with competitive inhibition and separation-of-function mutants

    PMID:21947006

    Open questions at the time
    • The identity of the endogenous mammalian cyclic dinucleotide was unknown
    • Structural basis of CDN recognition was unresolved
  4. 2012 High

    Reconstitution of the STING–TBK1–IRF3 signaling axis in vitro showed that STING's C-terminal region scaffolds both kinase and substrate, answering how signaling specificity is achieved.

    Evidence In vitro reconstitution with separation-of-function mutants disrupting IRF3 or TBK1 binding independently

    PMID:22394562

    Open questions at the time
    • Phosphorylation sites on STING required for IRF3 recruitment were not yet mapped
    • Higher-order oligomerization requirement was unknown
  5. 2013 High

    Identification of 2'3'-cGAMP as the endogenous second messenger, combined with crystal structures of ligand-bound STING, revealed the structural basis of the conformational 'closure' that activates STING and explained species-specific ligand preferences.

    Evidence Mass spectrometry, NMR, X-ray crystallography of STING–cGAMP complexes, gain-of-function mutagenesis (S162A)

    PMID:23722158 PMID:23747010 PMID:23910378

    Open questions at the time
    • Full-length structure including transmembrane domain was unresolved
    • Mechanism of ER-to-Golgi trafficking was unknown
  6. 2013 High

    Discovery that ULK1 phosphorylates STING to suppress IRF3 signaling after initial activation identified the first negative-feedback loop terminating STING-driven innate immunity.

    Evidence In vitro kinase assay, genetic knockouts, and autophagy/lysosome trafficking in mouse cells

    PMID:24119841

    Open questions at the time
    • Precise phosphorylation sites were incompletely mapped
    • Relationship between STING and autophagy beyond feedback was unclear
  7. 2014 High

    Gain-of-function TMEM173 mutations causing SAVI linked constitutive STING Golgi localization and signaling to human autoinflammatory disease, validating the trafficking-dependent activation model in a clinical setting.

    Evidence Patient genetic sequencing, constitutive Golgi localization by immunofluorescence, STAT1 phosphorylation assays, JAK inhibitor rescue

    PMID:25029335 PMID:25401470

    Open questions at the time
    • Molecular mechanism by which mutations bypass ligand requirement was not fully resolved
    • Therapeutic strategies beyond JAK inhibition were unexplored
  8. 2015 High

    Mapping of STING phosphorylation by TBK1/IKK and demonstration that phospho-STING recruits IRF3 via a conserved charge-based mechanism established phosphorylation of the adaptor itself as the specificity determinant for downstream transcription factor activation.

    Evidence Phosphopeptide binding assays and in vitro reconstitution across STING/MAVS/TRIF

    PMID:25636800

    Open questions at the time
    • Whether additional kinases contribute to STING phosphorylation remained open
  9. 2016 High

    Requirement of Cys88/91 palmitoylation at the Golgi for STING signaling established a lipid modification checkpoint that gates STING multimer assembly and downstream gene induction.

    Evidence Palmitoylation assay, 2-BP pharmacological inhibition, and Cys88/91 mutagenesis

    PMID:27324217

    Open questions at the time
    • Identity of the palmitoyl transferase was unknown
    • Relationship between palmitoylation and higher-order oligomerization was not structurally defined
  10. 2018 High

    Genetic epistasis showing that STING loss completely rescues inflammation and neurodegeneration in Parkin/PINK1-deficient mice placed STING as the critical effector of mitochondrial DNA-driven innate immune pathology downstream of impaired mitophagy.

    Evidence Double-knockout mouse models (Prkn−/−;Sting1−/−, Pink1−/−;Sting1−/−) with behavioral and inflammatory readouts

    PMID:30135585

    Open questions at the time
    • Whether cGAS is the exclusive sensor of escaped mtDNA in this context was not established
    • Relevance to human Parkinson's disease not directly tested
  11. 2018 High

    Identification of covalent STING antagonists targeting Cys91 and demonstration that palmitoylation is required for oligomeric complex formation at the Golgi linked the palmitoylation checkpoint to multimerization and provided pharmacological proof-of-concept for STING inhibition in autoinflammatory disease.

    Evidence Covalent inhibitor characterization, native PAGE/SEC for oligomerization, and in vivo mouse disease models

    PMID:29973723

    Open questions at the time
    • Long-term therapeutic window and off-target effects of Cys91-targeting inhibitors were not assessed
  12. 2018 High

    Discovery of a non-canonical STING signaling complex (IFI16–ATM–PARP1–p53–TRAF6) that activates NF-κB via K63-linked ubiquitination of STING, independent of cGAS, established a distinct DNA-damage-induced STING pathway.

    Evidence Co-IP, ubiquitination assays, genetic knockdown, and DNA-damage induction in human cells

    PMID:30193098

    Open questions at the time
    • Whether this pathway operates in vivo during physiological DNA damage remains unclear
    • The K63-ubiquitinated sites on STING were not mapped
  13. 2019 High

    Cryo-EM structures of full-length STING in inactive and cGAMP-bound states revealed that ligand binding induces a 180° LBD rotation driving tetramerization and higher-order oligomerization, and a companion structure of the TBK1–STING complex showed that the STING C-terminal tail inserts into the TBK1 dimer interface in a geometry requiring oligomerization for trans-phosphorylation.

    Evidence Cryo-EM of human/chicken STING apo and cGAMP-bound forms and STING–TBK1 complex, validated by structure-guided mutagenesis

    PMID:30842653 PMID:30842659

    Open questions at the time
    • Dynamic intermediate states during activation were not captured
    • Full-length human STING–TBK1 structure was obtained with chicken STING
  14. 2019 High

    Crystal structures and biochemical assays demonstrated that cGAMP closes the STING homodimer, releases the C-terminal tail, and exposes Cys148 for disulfide-linked polymerization, while disease-causing mutations constitutively release the tail—unifying gain-of-function disease mutations with the structural activation mechanism.

    Evidence X-ray crystallography, SAXS, disulfide crosslinking, and polymerization assays with SAVI-associated mutants

    PMID:31230712

    Open questions at the time
    • In vivo polymer stoichiometry and dynamics were not established
  15. 2019 High

    STING was shown to activate autophagy through a TBK1-independent, ULK/VPS34-independent but WIPI2/ATG5-dependent pathway using ERGIC-derived membranes for LC3 lipidation—establishing autophagy as an evolutionarily primordial STING function conserved from sea anemone to mammals.

    Evidence Autophagy flux assays in genetic knockouts, ERGIC fractionation, and cross-species comparison with sea anemone STING

    PMID:30842662

    Open questions at the time
    • Membrane curvature sensing mechanism at ERGIC was unknown
    • Cargo selectivity of STING-induced autophagosomes was incompletely defined
  16. 2020 High

    Multiple regulatory axes controlling STING turnover were defined: C9orf72 promotes lysosomal degradation of STING, OTUD5 deubiquitinase stabilizes STING by removing K48-ubiquitin, and GPX4-dependent redox homeostasis prevents C88 carbonylation that blocks ER-to-Golgi trafficking.

    Evidence Conditional knockouts (C9orf72, Otud5), carbonylation assays, in vivo disease models

    PMID:32541831 PMID:32814898 PMID:32879469

    Open questions at the time
    • Precise E3 ligases catalyzing K48-ubiquitination counteracted by OTUD5 were not identified
    • Quantitative thresholds for carbonylation-mediated STING inhibition were not determined
  17. 2021 High

    Discovery of STING ER membranous biocondensates showed that at high cGAMP concentrations STING phase-separates rather than translocates, sequestering TBK1 to prevent overactivation—revealing a concentration-dependent signaling rheostat.

    Evidence Live-cell fluorescence imaging, electron microscopy, and mutagenesis of condensation-deficient STING

    PMID:33833429

    Open questions at the time
    • Biophysical properties of the condensate (e.g., viscosity, exchange kinetics) were not characterized
    • Physiological cGAMP concentrations at which condensation dominates are unclear
  18. 2022 Medium

    Nuclear translocation of STING and direct interaction with the AHR transcription factor defined a non-canonical function independent of DNA sensing and autophagy, controlling gut microbial homeostasis.

    Evidence Nuclear fractionation, co-IP with domain mapping, mutagenesis, and mouse colitis models

    PMID:38016467

    Open questions at the time
    • Nuclear import mechanism for a multi-pass transmembrane protein is unresolved
    • Additional nuclear partners required for AHR activation are not identified
    • Independent replication is needed
  19. 2023 High

    Structural determination of autoinhibited apo-STING as a bilayer assembly and active cGAMP-bound STING as a curved filament explained how membrane topology change drives ER exit, while TAK1-mediated Ser355 phosphorylation was identified as a trafficking-permissive modification.

    Evidence Cryo-EM/X-ray of apo and active STING polymers, in vitro kinase assay for TAK1-S355, and in vivo tumor models

    PMID:37086726 PMID:37832545

    Open questions at the time
    • How COP-II machinery recognizes the curved STING filament is unknown
    • Interplay between S355 phosphorylation and other trafficking regulators is not fully mapped
  20. 2023 Medium

    Post-translational modification crosstalk was elaborated: ISGylation at K289 promotes STING oligomerization, HERC-mediated ISGylation at K150 competes with K48-ubiquitination to stabilize STING, RNF144A-mediated K6-ubiquitination at K236 promotes ER-to-Golgi trafficking, and SARS-CoV-2 PLpro cleaves ISGylation as an immune evasion strategy.

    Evidence ISGylation/ubiquitination assays, site-specific mutagenesis, knockout mice, SAVI patient cells, viral infection models

    PMID:37864791 PMID:37955227 PMID:38652662

    Open questions at the time
    • Whether K6-, K48-, K63-, and ISG15 modifications occur simultaneously or sequentially on a single STING molecule is unknown
    • Structural basis of how ISGylation at K289 promotes oligomerization is unresolved
  21. 2024 High

    A TBK1-independent primordial STING function in lysosomal biogenesis was defined: STING proton channel activity stimulates GABARAP lipidation, which activates TFEB in an mTORC1-independent manner—conserved across vertebrates—linking chronic sterile STING activation during aging to a cytoprotective lysosomal response.

    Evidence Proton channel mutagenesis, GABARAP lipidation assays, TFEB nuclear translocation, cross-species comparison (human/mouse/frog)

    PMID:39423796

    Open questions at the time
    • Structural basis of STING proton channel activity is unresolved
    • Whether TFEB activation counteracts or cooperates with interferon signaling in vivo is unclear
  22. 2025 High

    STING-induced CASM (conjugation of ATG8 to single membranes) was shown to activate LRRK2 kinase via GABARAP recruitment and to sequester FNIP-folliculin complexes to inhibit mTORC1, integrating STING autophagy with lysosomal stress responses and Parkinson's disease-associated kinase regulation.

    Evidence Genetic knockouts of ATG16L1/V-ATPase, LRRK2 kinase assays, FNIP pulldown, GABARAP-specific mutagenesis

    PMID:39812709 PMID:39982740

    Open questions at the time
    • Whether STING-LRRK2 axis contributes to LRRK2-associated Parkinson's pathogenesis is untested
    • How STING distinguishes between canonical autophagy and CASM outputs remains mechanistically unclear
  23. 2025 High

    Fumarate produced by hypoxia-activated ADSL was shown to directly bind STING and competitively inhibit cGAMP binding, establishing a metabolite-mediated immune evasion mechanism in tumors.

    Evidence Direct fumarate–STING binding assay, ADSL mutagenesis, in vivo tumor models

    PMID:40033100

    Open questions at the time
    • Whether other TCA metabolites similarly regulate STING is untested
    • Structural basis of fumarate occupancy in the CDN-binding pocket is not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Several major mechanistic questions remain: the structural basis of STING's proton channel activity, how STING achieves nuclear translocation despite being a multi-pass transmembrane protein, the identity of the palmitoyl transferase(s) acting on Cys88/91, and how cells distinguish between canonical IFN-inducing, NF-κB-activating, and autophagy/lysosomal STING outputs.
  • Proton channel structural mechanism unresolved
  • Nuclear import pathway for multi-pass TM protein unknown
  • Identity of STING palmitoyl transferase unknown
  • Decision logic for pathway-selective STING output undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0140299 molecular sensor activity 4 GO:0060089 molecular transducer activity 3 GO:0005215 transporter activity 1
Localization
GO:0005783 endoplasmic reticulum 5 GO:0005794 Golgi apparatus 4 GO:0005634 nucleus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 8 R-HSA-162582 Signal Transduction 6 R-HSA-392499 Metabolism of proteins 5 R-HSA-9612973 Autophagy 5 R-HSA-1643685 Disease 3 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-9609507 Protein localization 2 R-HSA-5357801 Programmed Cell Death 1
Partners
DDX41GABARAPIRF3OTUD5PTK2BTBK1TRAF6WIPI2
Complex memberships
IFI16–ATM–PARP1–TRAF6–STING complexSTING homodimer/oligomerSTING–TBK1 signaling complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 STING (stimulator of interferon genes) was identified as an ER-resident adaptor protein with five putative transmembrane regions that activates both NF-κB and IRF3 transcription pathways to induce type I interferons; loss of STING abrogated IFN-β induction by intracellular B-form DNA and herpesviruses; yeast two-hybrid and co-IP studies showed STING interacts with RIG-I and with SSR2/TRAPβ (a translocon-associated protein), implicating the translocon in innate signaling. Expression cloning, RNA interference knockdown, co-immunoprecipitation, yeast two-hybrid Nature High 18724357
2008 MITA (STING) was independently identified as a critical mediator of virus-triggered type I IFN signaling; it localizes to the outer mitochondrial membrane, associates with VISA/MAVS, interacts with IRF3, recruits TBK1 to the VISA-associated complex, and is phosphorylated by TBK1, which is required for MITA-mediated activation of IRF3. Expression cloning, co-immunoprecipitation, subcellular fractionation, knockdown/overexpression Immunity High 18818105
2009 ERIS (STING) resides exclusively on the ER membrane; its ER retention/retrieval sequence RIR is critical for ER localization and protein integrity; ERIS undergoes dimerization upon innate immune challenge, and coumermycin-induced forced dimerization leads to strong IFN induction, establishing that dimerization is critical for self-activation. Live imaging, subcellular fractionation, chemically induced dimerization, overexpression/knockdown Proceedings of the National Academy of Sciences of the United States of America High 19433799
2011 STING functions as a direct innate immune sensor of cyclic di-GMP: STING binds radiolabeled c-di-GMP directly, unlabeled cyclic dinucleotides compete for binding, and mutations in STING selectively impair the response to cyclic dinucleotides without affecting the DNA response, establishing a receptor function distinct from its adaptor role. Radioligand binding assay, competitive binding, mutagenesis, functional IFN assays Nature High 21947006
2011 DDX41 (a DEXDc helicase) acts as an intracellular DNA sensor that depends on STING to initiate signaling; DDX41 binds both DNA and STING, colocalizes with STING in the cytosol, and co-overexpression of DDX41 and STING has a synergistic effect on IFN-β promoter activity. Co-immunoprecipitation, shRNA knockdown, colocalization imaging, reporter assay Nature immunology High 21892174
2012 STING functions as a scaffold protein that recruits both TBK1 and IRF3 to specify phosphorylation of IRF3: an in vitro reconstitution system showed that the C-terminal region of STING is necessary and sufficient to activate TBK1 and stimulate IRF3 phosphorylation; mutations selectively disrupting STING–IRF3 binding abrogated IRF3 phosphorylation without impairing TBK1 activation. In vitro reconstitution, mutagenesis, co-immunoprecipitation Science signaling High 22394562
2013 cGAS produces a cyclic dinucleotide second messenger with a 2'-5' and 3'-5' phosphodiester linkage (2'3'-cGAMP) that binds STING and activates it; the 2'-5' linkage is required for potent activation of human STING, and cGAS first synthesizes a linear 2'-5'-linked dinucleotide that is then cyclized via a 3'-5' linkage. Mass spectrometry, NMR, enzymatic digestion, chemical synthesis, in vitro binding and functional assays Nature High 23722158
2013 Endogenous 2'3'-cGAMP contains two distinct phosphodiester linkages (2'-OH of GMP to 5'-phosphate of AMP, and 3'-OH of AMP to 5'-phosphate of GMP); crystal structure of STING bound to 2'3'-cGAMP revealed the structural basis for high-affinity binding and a ligand-induced conformational change in STING. X-ray crystallography, mass spectrometry, enzymatic linkage analysis, binding assays Molecular cell High 23747010
2013 Structure-function analysis of STING with c[G(2',5')pA(3',5')p] showed that human and mouse STING adopt a 'closed' conformation upon ligand binding; a point mutation S162A in the cyclic-dinucleotide-binding pocket of human STING rendered it sensitive to the otherwise mouse-specific drug DMXAA, validating the structural model. X-ray crystallography, mutagenesis, binding studies, functional IFN assays Cell High 23910378
2013 After STING activation and TBK1-mediated IRF3 signaling, STING is subsequently phosphorylated by ULK1/ATG1 (serine/threonine kinase), which suppresses IRF3 function; ULK1 activation occurs following dissociation from its repressor AMPK and is triggered by cGAS-produced CDNs, establishing a CDN-triggered negative-feedback loop to prevent sustained innate immune gene transcription. In vitro kinase assay, genetic knockouts, mutational analyses, autophagy/lysosome trafficking assays Cell High 24119841
2015 STING harbors conserved serine and threonine clusters that are phosphorylated by IKK and/or TBK1 following stimulation; phosphorylated STING binds a positively charged surface of IRF3 to recruit it for TBK1-mediated phosphorylation and activation, establishing phosphorylation of innate adaptor proteins as an essential conserved mechanism for selective IRF3 recruitment. In vitro reconstitution, mutagenesis, co-immunoprecipitation, phosphopeptide binding assays Science (New York, N.Y.) High 25636800
2014 Gain-of-function mutations in TMEM173 (STING) cause STING-associated vasculopathy with onset in infancy (SAVI); mutant STING spontaneously localizes to the Golgi (constitutive translocation), is constitutively active without exogenous cGAMP, leads to elevated STAT1 phosphorylation, and drives endothelial cell activation and apoptosis; JAK inhibitors reduced constitutive STAT1 phosphorylation in patient lymphocytes. Patient genetic sequencing, HEK293T reporter assays, cell stimulation assays, immunofluorescence, JAK inhibitor treatment The New England journal of medicine High 25029335 25401470
2016 Palmitoylation of STING at Cys88 and Cys91 at the Golgi is essential for STING activation; 2-bromopalmitate (palmitoylation inhibitor) suppresses palmitoylation and abolishes the type I IFN response; Cys88/91 mutation prevents palmitoylation and blocks STING-dependent host defense gene induction, including for constitutively active disease-associated STING variants. Palmitoylation assay, site-directed mutagenesis, 2-BP inhibitor treatment, IFN reporter assays Nature communications High 27324217
2018 Small-molecule antagonists covalently target transmembrane Cys91 of STING, blocking activation-induced palmitoylation; palmitoylation of STING is essential for its assembly into multimeric complexes at the Golgi and for recruitment of downstream signaling factors; these inhibitors reduce inflammatory cytokine production in human and mouse cells and attenuate autoinflammatory disease in mice. Covalent inhibitor characterization, palmitoylation assay, native PAGE/size-exclusion chromatography for oligomerization, in vivo mouse models Nature High 29973723
2019 Cryo-EM structure of full-length human and chicken STING in inactive dimeric state and cGAMP-bound chicken STING in dimeric and tetrameric states reveals: transmembrane and cytoplasmic regions form an integrated domain-swapped dimer; cGAMP binding induces 180° rotation of the ligand-binding domain relative to the transmembrane domain; this rotation drives a loop conformational change enabling STING tetramer and higher-order oligomer formation through side-by-side packing. Cryo-electron microscopy, structure-based mutagenesis, functional validation Nature High 30842659
2019 Cryo-EM structure of human TBK1 in complex with cGAMP-bound full-length chicken STING reveals: the C-terminal tail of STING adopts a β-strand-like conformation inserting into a groove between the kinase domain of one TBK1 subunit and the scaffold/dimerization domain of the second TBK1 subunit; the phosphorylation site Ser366 cannot reach the TBK1 active site in this conformation, indicating that STING phosphorylation requires oligomerization of both proteins; mutational analyses validate the binding mode. Cryo-electron microscopy, mutagenesis, functional TBK1/STING activation assays Nature High 30842653
2019 2'3'-cGAMP induces closing of the human STING homodimer and release of the STING C-terminal tail, exposing a polymerization interface leading to disulfide-linked polymer formation via Cys148; disease-causing hyperactive STING mutations either flank C148 (depending on disulfide formation) or reside in the C-terminal tail binding site (causing constitutive tail release and polymerization); bacterial c-di-GMP induces an alternative active conformation and acts as a partial antagonist of 2'3'-cGAMP signaling. X-ray crystallography, SAXS, disulfide crosslinking, biochemical polymerization assays, mutagenesis Cell High 31230712
2019 STING activates autophagy through a TBK1-independent mechanism: upon cGAMP binding, STING translocates to the ERGIC via COP-II and ARF GTPases; STING-containing ERGIC serves as a membrane source for LC3 lipidation through a pathway dependent on WIPI2 and ATG5 but independent of ULK and VPS34-beclin kinase complexes; cGAMP-induced autophagy clears cytosolic DNA and viruses; sea anemone STING induces autophagy but not interferons, suggesting autophagy is the primordial STING function. Fluorescence microscopy, autophagy flux assays, genetic knockouts, biochemical fractionation, evolutionary comparison Nature High 30842662
2018 PINK1- and parkin-mediated mitophagy restrains STING-dependent innate immunity; inflammation from exhaustive exercise or mtDNA mutation in Prkn-/- and Pink1-/- mice is completely rescued by concurrent loss of STING; dopaminergic neuron loss and motor defects in aged Prkn-/-;mutator mice are also rescued by STING loss, placing STING downstream of mitophagy failure as the driver of neuroinflammation. Genetic mouse models (double knockouts), exhaustive exercise model, mitochondrial mutator mice, behavioral testing Nature High 30135585
2020 GPX4 deficiency enhances lipid peroxidation, which leads to STING carbonylation at C88, inhibiting its trafficking from the ER to the Golgi complex and thereby specifically attenuating the cGAS-STING pathway; cellular redox homeostasis maintained by GPX4 is thus required for STING activation. GPX4 knockout/knockdown, lipid peroxidation assays, carbonylation assay, ER-to-Golgi trafficking assay Nature immunology High 32541831
2021 STING forms spherical ER membranous biocondensates (STING phase-separators) in DNA virus-infected or cGAMP-treated cells, requiring transmembrane domains, an intrinsically disordered region, and dimerization domain; intracellular cGAMP concentration determines STING translocation vs. condensation; STING biocondensates constrain STING and TBK1 acting as a 'sponge' to prevent immune overactivation; cells with STING-E336G/E337G show enhanced innate immune responses due to impaired condensation. Fluorescence live-cell imaging, electron microscopy, mutagenesis, TBK1 interaction assays, microtubule inhibitor treatment Nature cell biology High 33833429
2018 Non-canonical activation of STING by nuclear DNA damage is mediated by IFI16 together with ATM and PARP-1, independent of cGAS; this alternative STING signaling complex includes p53 and TRAF6; TRAF6 catalyzes K63-linked ubiquitination of STING, leading to NF-κB activation and an alternative STING-dependent gene expression program distinct from the IRF3-IFN program. Co-immunoprecipitation, ubiquitination assays, knockdown/knockout, reporter assays, DNA damage induction Molecular cell High 30193098
2020 C9orf72 in myeloid cells suppresses STING-mediated type I IFN signaling; C9orf72-/- myeloid cells are hyperresponsive to STING activators due to diminished autophagic/lysosomal degradation of STING; genetic loss of C9orf72 causes STING-dependent splenomegaly and autoinflammation rescuable by STING inhibition. Conditional knockout mice, macrophage stimulation assays, STING degradation assays, STING inhibitor treatment Nature High 32814898
2020 STING directly activates TBK1/IRF3 signaling, which induces PD-L1 in tumor monocytes via the IRF3-IFN-I axis; TLR2 stimulation remodels STING signaling by facilitating STING-TRAF6 interaction, suppressing the IRF3-IFN-I response while enhancing NF-κB activation, demonstrating context-dependent rewiring of STING signaling output. Co-immunoprecipitation, knockdown/overexpression, in vivo tumor models, flow cytometry Cancer cell Medium 40068600
2021 STING1 interacts with MTORC1 complex components and promotes MTORC1 complex formation in a SQSTM1-dependent manner upon palmitic acid stimulation; STING1 activation inhibits lipophagy, which is reversed by MTORC1 inhibition (rapamycin) or STING1 deficiency; this reveals a STING1-MTORC1 regulatory loop controlling hepatic lipid accumulation. Co-immunoprecipitation, STING1 knockout/overexpression MEFs, rapamycin treatment, lipophagy assays, patient tissue analysis Autophagy Medium 34382907
2022 STING1 directly interacts with MYD88, which blocks autophagic degradation of STING1 and causes IRF3/JUN-mediated ACOD1 gene transcription and itaconate production in myeloid cells; this STING1-MYD88 axis links TLR4 signaling to ACOD1 expression during septic shock; conditional myeloid-specific STING1 deletion fails to produce ACOD1/itaconate and protects against endotoxemia. Co-immunoprecipitation, conditional knockout mice, endotoxemia models, itaconate measurement iScience Medium 35769880
2022 STING1 nuclear localization drives activation of the transcription factor AHR independent of DNA sensing and autophagy; the cyclic dinucleotide binding domain of STING1 interacts with the AHR N-terminal domain; STING1-mediated AHR transcriptional activation requires additional nuclear partners; this function competitively inhibits cytoplasmic cGAS-STING1 signaling and controls gut microbiota composition. Nuclear fractionation, co-immunoprecipitation, mutagenesis, proteomics, mouse colitis models Immunity Medium 38016467
2023 Apo-STING forms a bilayer with head-to-head and side-by-side packing via its ligand-binding domain (LBD) that holds two ER membranes together, preventing STING ER exit and TBK1 recruitment (autoinhibited state); 2'3'-cGAMP-bound STING forms a filament structure with a bent monolayer assembly mediated by LBD and transmembrane domain; this curved active polymer deforms the ER membrane to support ER exit and anterograde transport. Cryo-EM, X-ray crystallography, biochemical ER exit assays, mutagenesis Molecular cell High 37086726
2023 TAK1 kinase (activated in a TAB1-dependent manner by STING signaling) directly phosphorylates STING at serine 355 prior to STING trafficking; this phosphorylation facilitates STING interaction with STEEP and promotes STING oligomerization and translocation to the ERGIC; TAK1 activation by TLR4 agonist boosts cGAMP-induced antitumor immunity in a STING-S355 phosphorylation-dependent manner. In vitro kinase assay, phospho-specific antibodies, co-immunoprecipitation, mouse allograft models, mutagenesis Molecular cell High 37832545
2023 NF-κB pathway activation (via TLR, IL-1R, TNFR, GF-R, or PKC signaling) enhances STING-mediated immune responses by inducing microtubule depolymerization; STING interacts with microtubules, and this interaction is critical for STING intracellular trafficking; NF-κB-induced microtubule depolymerization inhibits STING trafficking to lysosomes for degradation, prolonging active STING levels; gain-of-function STING mutations abolish the microtubule-STING interaction causing ligand-independent autoactivation. Co-immunoprecipitation, microtubule pulldown, live-cell trafficking assays, NF-κB pathway inhibitors/activators, mutagenesis Cell reports Medium 36857187
2023 STING directly interacts with WIPI2 via the PI3P-binding motif; STING-WIPI2 interaction is necessary for STING-induced autophagosome formation but does not affect STING activation or intracellular trafficking; STING-WIPI2 binding competes with PI3P for WIPI2, causing mutual inhibition between STING-induced autophagy and canonical PI3P-dependent autophagy; this STING-WIPI2 interaction is required for cytoplasmic DNA clearance and attenuation of cGAS-STING signaling. Co-immunoprecipitation, domain mapping, LC3 lipidation assays, autophagy flux assays, mutagenesis The EMBO journal High 36872914
2023 STING undergoes ISGylation at multiple lysine residues (K224, K236, K289, K347, K338, K370); ISGylation at K289 is crucial for STING oligomerization and type I IFN induction; inhibition of ISGylation at K289 suppresses STING-mediated IFN induction; removal of ISGylation alleviates gain-of-function SAVI phenotype. Co-immunoprecipitation, ISGylation assays, mutagenesis, molecular modeling, SAVI patient cells Cell reports Medium 37864791
2024 HERCs (HERC5 in humans, HERC6 in mice) mediate ISGylation of STING at K150, preventing its K48-linked ubiquitination and degradation; Herc6 deficiency suppresses HSV-1-induced type I IFN responses; SARS-CoV-2 papain-like protease cleaves HERC5-mediated ISGylation of STING to suppress antiviral responses, revealing an ISGylation-ubiquitination interplay at K150. ISGylation/ubiquitination assays, Herc6 knockout mice, viral infection assays, papain-like protease cleavage assay Cell reports Medium 38652662
2020 OTUD5 deubiquitinase interacts with STING, cleaves K48-linked polyubiquitin chains on STING, and promotes STING stability; OTUD5 knockout leads to faster STING turnover and impaired type I IFN signaling after cytosolic DNA stimulation; myeloid-specific Otud5 deletion increases susceptibility to HSV-1 infection and accelerates melanoma development. Co-immunoprecipitation, ubiquitination assay, conditional knockout mice, viral infection and tumor models Cellular & molecular immunology Medium 32879469
2023 RNF144A (RBR E3 ubiquitin ligase) interacts with STING and promotes K6-linked ubiquitination at K236, enhancing STING translocation from the ER to the Golgi and downstream signaling; the K236R STING mutant displays reduced innate immune signal transduction; Rnf144a-deficient cells show impaired DNA virus-triggered signaling and mice are more susceptible to DNA virus infection. Co-immunoprecipitation, ubiquitination assay, mutagenesis, Rnf144a knockout mice, viral infection models EMBO reports Medium 37955227
2022 UXT interacts with STING1 and promotes its autophagic degradation via SQSTM1 (p62); UXT is required to prevent excessive STING1-mediated type I IFN signaling; UXT facilitates SQSTM1-STING1 interaction for selective autophagy-mediated degradation; UXT deficiency exacerbates DNA virus infection and lupus models, and UXT replenishment suppresses IFN production in SLE patient PBMCs. Co-immunoprecipitation, autophagy assays, UXT conditional knockout mice, SLE patient samples Autophagy Medium 35543189
2023 STING interacts with NCOA4 (nuclear receptor coactivator 4), which mediates ferritinophagy (autophagic degradation of ferritin); STING promotes NCOA4-mediated ferritinophagy, leading to iron overload and lipid ROS accumulation (ferroptosis) in renal tubular cells during ischemic acute kidney injury; STING deficiency or pharmacological inhibition protects against AKI-related ferroptosis. Co-immunoprecipitation, STING knockout/overexpression, ferritinophagy assays, ischemia/reperfusion mouse model Free radical biology & medicine Medium 37634745
2024 STING has a TBK1-independent primordial function in lysosomal biogenesis: STING trafficking and its conserved proton channel activity stimulate GABARAP lipidation, which activates TFEB (a conserved regulator of lysosomal biogenesis) in an mTORC1-independent manner; this function is conserved across humans, mice, and frogs; TFEB supports cell survival during chronic sterile STING activation occurring in aging. Proteomics, proton channel mutagenesis, GABARAP lipidation assays, TFEB nuclear translocation assays, cross-species functional comparison Molecular cell High 39423796
2025 STING activation induces noncanonical autophagy (CASM) via formation of pH-elevated Golgi-derived vesicles in an ATG16L1- and V-ATPase-dependent manner; GABARAP lipidation inhibits mTORC1 by sequestering FNIP-folliculin complexes, activating MiT/TFE transcription factors (TFEB, TFE3, MITF) and lysosomal biogenesis; STING-induced autophagy also activates LRRK2 through GABARAPs and recruits ALIX-ESCRT machinery to mitigate endolysosomal perturbation. Genetic knockouts, ATG16L1/V-ATPase dependency assays, mTORC1 phosphorylation assays, FNIP pulldown, LRRK2 activity assays, ESCRT recruitment assays Proceedings of the National Academy of Sciences of the United States of America High 39982740
2025 STING activates LRRK2 at lysosomes via the CASM (conjugation of ATG8 to single membranes) pathway; GABARAP (not other ATG8 family members) is specifically required for LRRK2 lysosome recruitment and kinase activation downstream of STING; multiple stimuli that perturb lysosomal homeostasis converge on CASM to activate LRRK2. CASM assays, LRRK2 kinase activity assays, GABARAP-specific mutagenesis/knockouts, lysosomal recruitment imaging The Journal of cell biology High 39812709
2025 ADSL (adenylosuccinate lyase), a de novo purine synthesis enzyme, is phosphorylated at T350 by hypoxia-activated IKKβ, translocates to the ER, and interacts with STING; ADSL-produced fumarate directly binds STING and inhibits cGAMP binding to STING, blocking STING activation and downstream IRF3-dependent cytokine gene expression, enabling tumor immune evasion. Co-immunoprecipitation, fumarate-STING binding assay, mutagenesis, IKKβ kinase assays, in vivo tumor models, patient tissue analysis Nature cell biology High 40033100
2023 PTK2B (protein tyrosine kinase 2 beta) interacts with STING and promotes STING oligomerization in a kinase-independent manner; PTK2B also directly phosphorylates TBK1 at Tyr591 to increase TBK1 oligomerization and activation; Ptk2b-deficient mice are more susceptible to viral infection, establishing PTK2B as a positive regulator of STING-TBK1 signaling. Co-immunoprecipitation, in vitro kinase assay, oligomerization assays, Ptk2b knockout mice, viral infection models Nature communications Medium 37989995
2023 STING and PERK physically interact; STING agonists induce PERK activation in kidney tubule cells; mice with a STING activating mutation present with ER stress and kidney fibroinflammation; tubule-specific STING deletion protects against ER stress and kidney fibrosis, establishing STING as an upstream activator of PERK-mediated ER stress in kidney tubule cells. Co-immunoprecipitation, STING activating mutation mouse model, tubule-specific STING conditional knockout, PERK inhibitor treatment, transcriptomics Kidney international Medium 39566842
2021 During RNA virus (FMDV) infection, DDX58/RIG-I transmits signals to STING1, which activates EIF2AK3/PERK-dependent integrated stress response leading to reticulophagy and degradation of STING1 itself; STING1 polymerization (but not Golgi translocation or IFN activation) is necessary for FMDV-induced reticulophagy, demonstrating a non-canonical STING1 function in RNA virus infection. STING1 knockout/knockdown, STING1 mutants (translocation-deficient, polymerization-deficient), reticulophagy assays, EIF2AK3 inhibitors Autophagy Medium 34338134
2019 SPOP (E3 ubiquitin ligase adaptor) targets and destabilizes STING1 protein; prostate cancer-associated SPOP mutations result in upregulated non-canonical STING1-NF-κB signaling; PARP inhibitor treatment shifts SPOP-mutant CRPC from immunosuppressive NC-STING-NF-κB toward canonical cGAS-STING-IFNβ signaling. Co-immunoprecipitation, proteomics, SPOP-mutant cell line models, in vivo allograft models Clinical cancer research Medium 37581614

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 2894 18724357
2021 The cGAS-STING pathway as a therapeutic target in inflammatory diseases. Nature reviews. Immunology 1722 33833439
2015 Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science (New York, N.Y.) 1601 25636800
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2013 cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING. Nature 1392 23722158
2010 IFI16 is an innate immune sensor for intracellular DNA. Nature immunology 1363 20890285
2011 STING is a direct innate immune sensor of cyclic di-GMP. Nature 1295 21947006
2008 The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 1278 18818105
2014 Activated STING in a vascular and pulmonary syndrome. The New England journal of medicine 1107 25029335
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2012 STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. Science signaling 1078 22394562
2015 STING: infection, inflammation and cancer. Nature reviews. Immunology 1071 26603901
2018 Parkin and PINK1 mitigate STING-induced inflammation. Nature 1057 30135585
2019 Autophagy induction via STING trafficking is a primordial function of the cGAS pathway. Nature 1039 30842662
2018 Targeting STING with covalent small-molecule inhibitors. Nature 929 29973723
2013 Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Molecular cell 890 23747010
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2019 Structural basis of STING binding with and phosphorylation by TBK1. Nature 849 30842653
2020 TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS. Cell 787 33031745
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2011 The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells. Nature immunology 736 21892174
2009 ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization. Proceedings of the National Academy of Sciences of the United States of America 729 19433799
2023 cGAS-STING drives ageing-related inflammation and neurodegeneration. Nature 709 37532932
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2018 Design of amidobenzimidazole STING receptor agonists with systemic activity. Nature 684 30405246
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2020 Structures and Mechanisms in the cGAS-STING Innate Immunity Pathway. Immunity 647 32668227
2013 The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING. Cell reports 641 23707065
2019 Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP. Nature 604 30842659
2013 Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling. Cell 581 24119841
2016 Activation of STING requires palmitoylation at the Golgi. Nature communications 573 27324217
2021 Amplifying STING activation by cyclic dinucleotide-manganese particles for local and systemic cancer metalloimmunotherapy. Nature nanotechnology 541 34594005
2018 Non-canonical Activation of the DNA Sensing Adaptor STING by ATM and IFI16 Mediates NF-κB Signaling after Nuclear DNA Damage. Molecular cell 537 30193098
2019 STING-IRF3 contributes to lipopolysaccharide-induced cardiac dysfunction, inflammation, apoptosis and pyroptosis by activating NLRP3. Redox biology 513 31121492
2013 Structure-function analysis of STING activation by c[G(2',5')pA(3',5')p] and targeting by antiviral DMXAA. Cell 494 23910378
2022 The cGAS-STING pathway and cancer. Nature cancer 485 36510011
2020 cGAS-STING, an important pathway in cancer immunotherapy. Journal of hematology & oncology 477 32571374
2019 Mitochondrial Damage Causes Inflammation via cGAS-STING Signaling in Acute Kidney Injury. Cell reports 472 31665638
2022 The cGAS-STING pathway drives type I IFN immunopathology in COVID-19. Nature 452 35045565
2014 Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. The Journal of clinical investigation 449 25401470
2016 The cGAS-STING Defense Pathway and Its Counteraction by Viruses. Cell host & microbe 351 26867174
2020 Redox homeostasis maintained by GPX4 facilitates STING activation. Nature immunology 344 32541831
2019 STING Polymer Structure Reveals Mechanisms for Activation, Hyperactivation, and Inhibition. Cell 329 31230712
2021 STING Agonists as Cancer Therapeutics. Cancers 321 34070756
2022 Cellular functions of cGAS-STING signaling. Trends in cell biology 316 36437149
2017 Crosstalk between Cytoplasmic RIG-I and STING Sensing Pathways. Trends in immunology 282 28073693
2020 cGAS-STING pathway in cancer biotherapy. Molecular cancer 280 32887628
2020 Signaling by cGAS-STING in Neurodegeneration, Neuroinflammation, and Aging. Trends in neurosciences 243 33187730
2020 C9orf72 in myeloid cells suppresses STING-induced inflammation. Nature 237 32814898
2017 Evolutionary Origins of cGAS-STING Signaling. Trends in immunology 223 28416447
2020 Trial watch: STING agonists in cancer therapy. Oncoimmunology 222 32934881
2007 A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. American journal of human genetics 207 17846994
2021 The STING1 network regulates autophagy and cell death. Signal transduction and targeted therapy 205 34078874
2020 PRMT5 control of cGAS/STING and NLRC5 pathways defines melanoma response to antitumor immunity. Science translational medicine 194 32641491
2020 The interactions between cGAS-STING pathway and pathogens. Signal transduction and targeted therapy 177 32532954
2021 The STING phase-separator suppresses innate immune signalling. Nature cell biology 172 33833429
2023 NF-κB activation enhances STING signaling by altering microtubule-mediated STING trafficking. Cell reports 155 36857187
2013 The cGAS-STING pathway for DNA sensing. Molecular cell 141 23870141
2021 Delivery of STING agonists for adjuvanting subunit vaccines. Advanced drug delivery reviews 137 34756942
2018 SnapShot: CGAS-STING Signaling. Cell 131 29570996
2024 The balance of STING signaling orchestrates immunity in cancer. Nature immunology 93 38918609
2023 STING promotes ferroptosis through NCOA4-dependent ferritinophagy in acute kidney injury. Free radical biology & medicine 88 37634745
2021 The STING antagonist H-151 ameliorates psoriasis via suppression of STING/NF-κB-mediated inflammation. British journal of pharmacology 88 34460100
2021 Lipotoxicity-induced STING1 activation stimulates MTORC1 and restricts hepatic lipophagy. Autophagy 87 34382907
2020 OTUD5 promotes innate antiviral and antitumor immunity through deubiquitinating and stabilizing STING. Cellular & molecular immunology 85 32879469
2019 A STING to inflammation and autoimmunity. Journal of leukocyte biology 79 30990921
2024 Mitophagy and cGAS-STING crosstalk in neuroinflammation. Acta pharmaceutica Sinica. B 72 39220869
2017 Regulating STING in health and disease. Journal of inflammation (London, England) 72 28596706
2021 STING-Mediated Lung Inflammation and Beyond. Journal of clinical immunology 70 33532887
2022 cGAS-STING signaling. Current biology : CB 68 35820380
2022 Activation of Stimulator of IFN Genes (STING) Causes Proteinuria and Contributes to Glomerular Diseases. Journal of the American Society of Nephrology : JASN 65 36198430
2025 Regulation of the cGAS-STING Pathway. Annual review of immunology 63 40085836
2023 Targeting STING oligomerization with small-molecule inhibitors. Proceedings of the National Academy of Sciences of the United States of America 63 37549268
2023 The mechanism of STING autoinhibition and activation. Molecular cell 61 37086726
2019 Neuroinflammation and the cGAS-STING pathway. Journal of neurophysiology 60 30673358
2023 STING directly recruits WIPI2 for autophagosome formation during STING-induced autophagy. The EMBO journal 58 36872914
2022 Nanodelivery of cGAS-STING activators for tumor immunotherapy. Trends in pharmacological sciences 55 36089410
2021 The Evolution of STING Signaling and Its Involvement in Cancer. Trends in biochemical sciences 53 33461879
2025 Targeting tumor monocyte-intrinsic PD-L1 by rewiring STING signaling and enhancing STING agonist therapy. Cancer cell 50 40068600
2023 Regulation of cGAS and STING signaling during inflammation and infection. The Journal of biological chemistry 50 37247757
2020 cGAS-STING pathway in oncogenesis and cancer therapeutics. Oncotarget 49 32774773
2021 Zebularine elevates STING expression and enhances cGAMP cancer immunotherapy in mice. Molecular therapy : the journal of the American Society of Gene Therapy 47 33571681
2023 Nanoparticle-Mediated STING Activation for Cancer Immunotherapy. Advanced healthcare materials 46 36905358
2025 Self-Cascaded Pyroptosis-STING Initiators for Catalytic Metalloimmunotherapy. Journal of the American Chemical Society 45 39818788
2023 SARS-CoV-2 nonstructural protein 6 triggers endoplasmic reticulum stress-induced autophagy to degrade STING1. Autophagy 45 37482689
2023 Development of LB244, an Irreversible STING Antagonist. Journal of the American Chemical Society 45 37695732
2021 The role of cGAS/STING in intestinal immunity. European journal of immunology 45 33577080
2020 Molecular and spatial mechanisms governing STING signalling. The FEBS journal 44 33237620
2022 UXT attenuates the CGAS-STING1 signaling by targeting STING1 for autophagic degradation. Autophagy 43 35543189
2022 The STING1-MYD88 complex drives ACOD1/IRG1 expression and function in lethal innate immunity. iScience 42 35769880
2020 Targeting of the cGAS-STING system by DNA viruses. Biochemical pharmacology 42 32004549
2020 Structural Insights into STING Signaling. Trends in cell biology 42 32302551
2024 A TBK1-independent primordial function of STING in lysosomal biogenesis. Molecular cell 41 39423796
2023 Editorial: A Rapid Global Increase in COVID-19 is Due to the Emergence of the EG.5 (Eris) Subvariant of Omicron SARS-CoV-2. Medical science monitor : international medical journal of experimental and clinical research 41 37654205
2019 Bioactive modulators targeting STING adaptor in cGAS-STING pathway. Drug discovery today 41 31758915
2024 Understanding and therapeutically exploiting cGAS/STING signaling in glioblastoma. The Journal of clinical investigation 40 38226619
2024 Agonists and Inhibitors of the cGAS-STING Pathway. Molecules (Basel, Switzerland) 40 38999073
2023 Targeting STING in cancer: Challenges and emerging opportunities. Biochimica et biophysica acta. Reviews on cancer 40 37717857
2023 TAK1 is an essential kinase for STING trafficking. Molecular cell 40 37832545
2025 A STING-CASM-GABARAP pathway activates LRRK2 at lysosomes. The Journal of cell biology 37 39812709
2022 Activation of STING Based on Its Structural Features. Frontiers in immunology 37 35928815
2020 cGAS/STING: novel perspectives of the classic pathway. Molecular biomedicine 37 35006429
2023 Updated roles of cGAS-STING signaling in autoimmune diseases. Frontiers in immunology 35 37781360
2023 Regulation of STING activity in DNA sensing by ISG15 modification. Cell reports 35 37864791
2023 Nuclear localization of STING1 competes with canonical signaling to activate AHR for commensal and intestinal homeostasis. Immunity 35 38016467
2024 Ginkgetin Alleviates Inflammation and Senescence by Targeting STING. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 34 39558862
2025 STING-induced noncanonical autophagy regulates endolysosomal homeostasis. Proceedings of the National Academy of Sciences of the United States of America 33 39982740
2022 Control of innate immunity by the cGAS-STING pathway. Immunology and cell biology 33 35485309
2023 Huangkui capsule attenuates diabetic kidney disease through the induction of mitophagy mediated by STING1/PINK1 signaling in tubular cells. Phytomedicine : international journal of phytotherapy and phytopharmacology 31 37517171
2023 Stimulator of interferon genes (STING): Key therapeutic targets in ischemia/reperfusion injury. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 31 37699319
2024 ER: a critical hub for STING signaling regulation. Trends in cell biology 30 38423853
2021 STING1 is essential for an RNA-virus triggered autophagy. Autophagy 29 34338134
2021 The HMGB1-AGER-STING1 pathway mediates the sterile inflammatory response to alkaliptosis. Biochemical and biophysical research communications 28 33992959
2021 STING1 in sepsis: Mechanisms, functions, and implications. Chinese journal of traumatology = Zhonghua chuang shang za zhi 28 34334261
2024 STING inhibitors sensitize platinum chemotherapy in ovarian cancer by inhibiting the CGAS-STING pathway in cancer-associated fibroblasts (CAFs). Cancer letters 27 38373690
2024 The critical role of endoplasmic reticulum stress and the stimulator of interferon genes (STING) pathway in kidney fibrosis. Kidney international 27 39566842
2023 Potential Therapeutic Value of the STING Inhibitors. Molecules (Basel, Switzerland) 27 37049889
2023 Gelsevirine is a novel STING-specific inhibitor and mitigates STING-related inflammation in sepsis. Frontiers in immunology 27 37583703
2023 SIRT2 negatively regulates the cGAS-STING pathway by deacetylating G3BP1. EMBO reports 27 37870259
2020 When STING Meets Viruses: Sensing, Trafficking and Response. Frontiers in immunology 27 33133062
2023 RNF144A promotes antiviral responses by modulating STING ubiquitination. EMBO reports 26 37955227
2025 MLKL activates the cGAS-STING pathway by releasing mitochondrial DNA upon necroptosis induction. Molecular cell 25 40614706
2024 ISGylation by HERCs facilitates STING activation. Cell reports 25 38652662
2022 Emerging dimensions of cellular cGAS-STING signaling. Current opinion in immunology 25 35124516
2021 Nanodelivery of STING agonists against cancer and infectious diseases. Molecular aspects of medicine 25 34353637
2020 Balancing STING in antimicrobial defense and autoinflammation. Cytokine & growth factor reviews 24 32563552
2025 ADSL-generated fumarate binds and inhibits STING to promote tumour immune evasion. Nature cell biology 22 40033100
2023 SPOP Mutations Target STING1 Signaling in Prostate Cancer and Create Therapeutic Vulnerabilities to PARP Inhibitor-Induced Growth Suppression. Clinical cancer research : an official journal of the American Association for Cancer Research 22 37581614
2022 Chemical regulation of the cGAS-STING pathway. Current opinion in chemical biology 21 35753220
2023 PTK2B promotes TBK1 and STING oligomerization and enhances the STING-TBK1 signaling. Nature communications 20 37989995