Affinage

AIM2

Interferon-inducible protein AIM2 · UniProt O14862

Length
343 aa
Mass
39.0 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AIM2 is a cytosolic double-stranded DNA sensor that functions as the scaffold of a canonical inflammasome and also performs inflammasome-independent signaling roles in tumor suppression, T-cell metabolism, and neurodevelopment. Its HIN200 domain binds dsDNA in a duplex-length-dependent manner, nucleating ordered helical filaments whose pyrin domain in turn templates ASC filament polymerization to recruit and activate caspase-1, driving IL-1β/IL-18 maturation and gasdermin-D-dependent pyroptosis; AIM2 can also participate in a multi-sensor PANoptosome complex with pyrin and ZBP1 that simultaneously engages pyroptosis, apoptosis, and necroptosis (PMID:19158675, PMID:36864667, PMID:28813641, PMID:34471287). Independent of inflammasome assembly, AIM2 physically interacts with DNA-PK to restrain Akt activation in intestinal epithelium, and with the RACK1–PP2A phosphatase complex to attenuate Akt/mTOR signaling and glycolysis in regulatory T cells, thereby stabilizing Treg identity and suppressing colorectal tumorigenesis (PMID:26107252, PMID:33505023). AIM2 protein abundance is positively regulated by USP21-mediated deubiquitination that stabilizes it and permits ASC complex formation, and negatively regulated by TRIM11-dependent ubiquitination coupled to p62-selective autophagy (PMID:34470856, PMID:27498865).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2009 High

    The identity of the cytosolic dsDNA sensor upstream of caspase-1 was unknown; domain mapping and knockdown showed that AIM2's HIN200 domain binds dsDNA while its pyrin domain recruits ASC to activate caspase-1, establishing AIM2 as the founding dsDNA inflammasome sensor.

    Evidence Knockdown in mouse/human cells with domain-function mapping (HIN200 vs. pyrin) and caspase-1/NF-κB assays

    PMID:19158675

    Open questions at the time
    • Structural basis of DNA recognition and filament assembly not yet resolved
    • Mechanism by which DNA length determines activation unknown
    • In vivo physiological role not demonstrated
  2. 2013 High

    Whether AIM2 inflammasome activation produces only pyroptosis was unclear; demonstration that ASC specks recruit and activate caspase-8 alongside caspase-1 established that AIM2 inflammasomes can simultaneously drive pyroptosis and apoptosis.

    Evidence Live-cell imaging showing procaspase-8 localization to ASC specks, direct pyrin domain binding, and quantification of pyroptosis vs. apoptosis

    PMID:23645208

    Open questions at the time
    • Whether caspase-8 is engaged in all cell types unknown
    • Relative contribution of each death pathway in vivo unresolved
  3. 2014 Medium

    The relationship between AIM2 inflammasomes and the microtubule/autophagy machinery was undefined; EB1 depletion and imaging showed that AIM2 inflammasomes associate with microtubule-organizing centers and rely on EB1 for autophagy-dependent unconventional IL-1β secretion.

    Evidence EB1 knockdown, live-cell colocalization with MTOCs and autophagosomes, LC3-dependent secretion assays

    PMID:25164813

    Open questions at the time
    • Direct AIM2–EB1 physical interaction not shown in this study
    • AMPK-EB1 regulatory link mechanistically incomplete
    • Relevance beyond macrophages unconfirmed
  4. 2015 High

    AIM2 was considered solely a pro-inflammatory innate immune sensor; interaction with DNA-PK and suppression of Akt activation in intestinal epithelium revealed an inflammasome-independent tumor suppressor function, explaining increased colon tumorigenesis in Aim2-knockout mice.

    Evidence Reciprocal Co-IP of AIM2–DNA-PK, Aim2−/− and Asc−/− mouse tumor models (AOM/DSS, APC-Min), Akt inhibitor rescue, bone-marrow chimeras

    PMID:26107252

    Open questions at the time
    • Structural basis of AIM2–DNA-PK interaction not defined
    • Whether DNA-PK kinase activity is directly blocked or indirectly modulated unresolved
  5. 2016 High

    How AIM2 protein levels are negatively regulated was unknown; TRIM11 was identified as an E3 ligase that ubiquitinates itself at K458 upon AIM2 binding, recruiting p62 for selective autophagic degradation of AIM2 and thereby limiting inflammasome activation.

    Evidence Co-IP, ubiquitination assays with K458 mutagenesis, siRNA, autophagy flux assays

    PMID:27498865

    Open questions at the time
    • Ubiquitination sites on AIM2 itself not mapped
    • Tissue-specific regulation of TRIM11–AIM2 axis not established
  6. 2016 High

    Whether AIM2 antagonizes the cGAS–STING type I IFN pathway was unresolved; experiments in AIM2-deficient cells showed markedly enhanced cGAMP, STING aggregation, and IFN-β, establishing that AIM2-driven pyroptosis limits STING pathway activation by eliminating the DNA-sensing cell.

    Evidence AIM2−/−, ASC−/−, and caspase-1−/− cells with cGAMP quantification, STING aggregation, TBK1/IRF3 phosphorylation

    PMID:26927800

    Open questions at the time
    • Whether AIM2 also directly competes with cGAS for DNA not biochemically proven
    • Cell-type differences in this antagonism not systematically explored
  7. 2017 High

    The three-dimensional architecture of the inflammasome filament was undefined; X-ray crystallography and cryo-EM revealed that AIM2 PYD nucleates helical ASC PYD filaments, which in turn template caspase-1 CARD filaments, establishing nucleated polymerization as the assembly mechanism.

    Evidence X-ray crystallography and cryo-EM of AIM2–ASC–caspase-1 filament intermediates

    PMID:28813641

    Open questions at the time
    • Full-length AIM2 filament structure on dsDNA not determined at high resolution
    • Stoichiometry of AIM2:DNA in physiological settings unknown
  8. 2017 Medium

    Whether viruses directly neutralize AIM2 was unconfirmed; HCMV tegument protein pUL83 was shown to interact with AIM2 in the cytoplasm during early infection, reducing inflammasome protein expression and activation.

    Evidence Co-IP, yeast two-hybrid, immunofluorescence in infected macrophages and reconstituted HEK293T system

    PMID:28219398

    Open questions at the time
    • pUL83 binding interface on AIM2 not mapped
    • Whether other herpesviruses use analogous evasion mechanisms not tested
    • Functional consequence limited to reconstituted system
  9. 2020 High

    AIM2's role in normal development was unknown; demonstration that AIM2 purges DNA-damaged neural precursors via gasdermin-D-dependent pyroptosis (but not IL-1/IL-18) during neurodevelopment established a physiological quality-control function for the inflammasome.

    Evidence Aim2−/− and Gsdmd−/− mice, DNA-damage agents, BrdU incorporation, behavioral assays

    PMID:32350463

    Open questions at the time
    • Source of endogenous DNA damage triggering AIM2 in neural progenitors not identified
    • Whether this extends to non-CNS developmental contexts unknown
  10. 2021 High

    How AIM2 protein stability is positively regulated was unclear; USP21 was identified as a deubiquitinase that binds AIM2 upon DNA stimulation, removes ubiquitin to prevent proteasomal degradation, and is specifically required for AIM2–ASC complex formation but not DNA binding.

    Evidence Co-IP, deubiquitination assays, USP21 depletion, proteasome inhibition, DNA-binding and ASC-assembly assays

    PMID:34470856

    Open questions at the time
    • Ubiquitin chain type(s) removed by USP21 not defined
    • Whether USP21 regulation is stimulus-specific not explored
  11. 2021 High

    Whether AIM2 functions outside innate immunity in T cells was unknown; conditional knockout revealed that AIM2 interacts with the RACK1–PP2A phosphatase complex in Treg cells to restrain Akt/mTOR/MYC signaling and glycolysis, promoting Treg stability independently of inflammasome activation.

    Evidence T cell-conditional AIM2 KO, Co-IP of AIM2–RACK1–PP2A, RNA-seq, metabolic profiling, lineage tracing

    PMID:33505023

    Open questions at the time
    • Whether AIM2 directly bridges RACK1 to PP2A or acts allosterically unresolved
    • Whether DNA binding is required for this T-cell function unclear
  12. 2021 High

    Whether AIM2 participates in multi-sensor complexes beyond the canonical ASC inflammasome was unknown; Co-IP of a PANoptosome containing AIM2, pyrin, ZBP1, ASC, caspase-1, caspase-8, RIPK3, RIPK1, and FADD established that AIM2 co-assembles with other sensors to drive simultaneous pyroptosis, apoptosis, and necroptosis.

    Evidence Reciprocal Co-IP, Aim2−/−/ZBP1−/−/Pyrin−/− cells, cell death pathway dissection, HSV-1 and Francisella in vivo models

    PMID:34471287

    Open questions at the time
    • Architecture and hierarchy of sensor engagement within the PANoptosome not structurally resolved
    • Whether all components are simultaneously present or assembled sequentially unknown
  13. 2021 High

    AIM2's role in epithelial cell migration was undefined; demonstration that STAT3-induced AIM2 binds EB1 to promote gastric epithelial migration and tumorigenesis independent of inflammasome activation established a non-immune, pro-migratory scaffolding function.

    Evidence AIM2–EB1 Co-IP in vivo and in vitro, AIM2 genetic targeting in gp130F/F mouse model, xenograft

    PMID:34489308

    Open questions at the time
    • Binding interface between AIM2 and EB1 not mapped
    • Whether this applies to migration in non-gastric epithelia not tested
  14. 2023 High

    The basis of AIM2's nucleic acid selectivity was mechanistically unclear; in vitro reconstitution and cryo-EM showed that AIM2 forms ordered filaments only on dsDNA of sufficient length, and that disordered oligomers on non-dsDNA substrates fail to nucleate ASC polymerization, establishing filament order as the specificity checkpoint.

    Evidence In vitro binding with diverse nucleic acid substrates, cryo-EM of filaments, ASC polymerization assays

    PMID:36864667

    Open questions at the time
    • Minimum dsDNA length threshold for productive filament formation not precisely defined
    • Whether post-translational modifications tune this threshold unknown
  15. 2023 High

    Transcriptional regulation of AIM2 by other inflammasome sensors was uncharacterized; ChIP-PCR showed that NLRP3 deficiency leads to SREBF1 upregulation, which directly binds the Aim2 promoter to increase AIM2 expression and pyroptosis in uveitis, revealing cross-regulation between NLRP3 and AIM2 inflammasomes.

    Evidence Nlrp3−/− mice, ChIP-PCR (SREBF1 on Aim2 promoter), Aim2−/− mice, SREBF1 silencing, RNA-seq

    PMID:36529965

    Open questions at the time
    • Whether NLRP3-SIK1-SREBF1-AIM2 axis operates in cell types beyond ocular macrophages unknown
    • Direct phosphorylation targets of SIK1 in this context not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: the high-resolution structure of full-length AIM2 filaments assembled on physiological DNA in cells; the molecular determinants distinguishing AIM2's inflammasome-dependent from inflammasome-independent functions; and how tissue- and cell-type-specific post-translational regulation (ubiquitination, deubiquitination) integrates with transcriptional control to tune AIM2 activity in homeostasis versus disease.
  • Full-length AIM2–DNA filament structure at atomic resolution lacking
  • No unified model for how AIM2 toggles between inflammasome-dependent and -independent modes
  • Systematic mapping of AIM2 ubiquitination sites and chain types in primary cells not performed

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 3
Partners
ASCCASP1DNA-PKCSEB1PP2ARACK1TRIM11USP21
Complex memberships
AIM2 inflammasome (AIM2–ASC–caspase-1)AIM2–pyrin–ZBP1 PANoptosomeRACK1–PP2A complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 AIM2 HIN200 domain binds cytosolic dsDNA, while its pyrin domain associates with the adaptor ASC to activate caspase-1 and NF-κB; knockdown of Aim2 abrogates caspase-1 activation in response to cytoplasmic dsDNA and vaccinia virus, establishing AIM2 as a cytosolic DNA receptor that forms a caspase-1-activating inflammasome with ASC. Knockdown experiments in mouse and human cells, domain-function mapping (HIN200 vs. pyrin domain), caspase-1 activity assays, NF-κB reporter assays Nature High 19158675
2013 AIM2 and NLRP3 inflammasomes activate both caspase-1 (pyroptosis) and caspase-8 (apoptosis) via ASC; procaspase-8 localizes to ASC inflammasome specks and binds directly to the pyrin domain of ASC, making caspase-8 an integral inflammasome component. Gene knockdown, live-cell imaging, co-localization of procaspase-8 with ASC specks, direct binding assay (pyrin domain of ASC), pyroptosis vs. apoptosis quantification at varying DNA concentrations Cell death and differentiation High 23645208
2015 In resting cells, AIM2 physically interacts with and limits activation of DNA-dependent protein kinase (DNA-PK), a PI3K-related kinase that promotes Akt phosphorylation; loss of AIM2 promotes DNA-PK-mediated Akt activation to enhance tumor growth, independent of inflammasome activation. Co-immunoprecipitation, Aim2-/- and Asc-/- mouse tumor models (AOM/DSS and APC-Min), Akt inhibitor rescue, bone-marrow chimera studies Nature medicine High 26107252
2016 TRIM11 binds AIM2 via its PS domain and undergoes auto-polyubiquitination at K458, promoting association with the autophagic cargo receptor p62 to mediate AIM2 degradation via selective autophagy, thereby suppressing AIM2 inflammasome activation. Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis (K458), siRNA knockdown, autophagy flux assays Cell reports High 27498865
2016 PKM2-mediated glycolysis promotes AIM2 inflammasome activation through EIF2AK2 phosphorylation in macrophages; pharmacological or genetic inhibition of PKM2 or EIF2AK2 attenuates AIM2 inflammasome activation and IL-1β/IL-18 release. PKM2 conditional knockout in myeloid cells, pharmacologic inhibition, EIF2AK2 knockdown, IL-1β/IL-18 ELISA, in vivo sepsis models Nature communications High 27779186
2017 25-hydroxycholesterol (25-HC) produced by macrophage cholesterol-25-hydroxylase (Ch25h) prevents AIM2 inflammasome activation; Ch25h deficiency causes cholesterol accumulation, which reduces mitochondrial respiratory capacity and releases mitochondrial DNA into the cytosol to activate AIM2; AIM2 deficiency rescues the increased inflammasome activity of Ch25h-/- macrophages. Ch25h-/- and Aim2-/- macrophages, mitochondrial function assays, cytosolic mtDNA quantification, IL-1β secretion assays, genetic epistasis Cell High 29033131
2017 HCMV tegument protein pUL83 directly interacts with AIM2 in the cytoplasm during early infection; the pUL83/AIM2 interaction reduces expression and activation of AIM2 inflammasome-associated proteins, constituting a viral immune evasion mechanism. Co-immunoprecipitation, yeast two-hybrid, immunofluorescence co-localization, reconstituted HEK293T inflammasome system with pUL83 expression Virology journal Medium 28219398
2017 AIM2 inflammasome activation by influenza A virus (IAV) results from IAV-induced dsDNA release and caspase-1 activation in macrophages specifically; AIM2-deficient mice show attenuated lung injury with improved survival but unaltered viral burden and adaptive immunity, establishing a macrophage-specific AIM2 function in IAV-induced lung injury. Aim2-/- mice, AIM2-specific siRNA in human/mouse alveolar macrophages and type II cells, caspase-1 activation assays, in vivo influenza challenge Journal of immunology High 28424239
2018 AIM2 inflammasome is activated in macrophages that engulf DNA from necrotic cells; DNA uptake occurs in large vacuolar structures within recruited macrophages; DNase I treatment attenuates IL-1β levels, confirming dsDNA as the principal DAMP; AIM2-dependent caspase-1 activation and ASC speck formation drive a proinflammatory phenotype contributing to CKD progression. Bone marrow chimera studies, intravital microscopy, Aim2-/- mice, in vitro macrophage engulfment assays with DNase I treatment, caspase-1 activity assays, ASC speck imaging Journal of the American Society of Nephrology High 29439156
2019 AIM2 antagonizes IFI205-mediated type I IFN induction by sequestering IFI205 away from STING, revealing AIM2 as a negative regulator of the interferon response to cytosolic retrotransposon DNA. Aim2-knockout macrophages, cGAMP measurement, STING aggregation assays, ALR-complementation experiments mBio Medium 28679751
2016 AIM2 deficiency in dendritic cells and macrophages leads to markedly higher IFN-β production in response to DNA via enhanced cGAMP generation, STING aggregation, and TBK1/IRF3 phosphorylation; AIM2-induced pyroptosis (caspase-1-dependent cell death) is a major mechanism suppressing STING pathway activation. AIM2-/-, ASC-/-, and caspase-1-/- cells, cGAMP measurement, STING aggregation assays, TBK1/IRF3 phosphorylation, caspase-1 inhibition Journal of immunology High 26927800
2014 HMGB1-DNA complex initially activates AIM2-dependent inflammasome and IL-1β release via RAGE receptor; subsequently, HMGB1-DNA triggers ATG5-dependent autophagy that limits AIM2 inflammasome activation, identifying autophagy as a negative counter-regulatory mechanism. RAGE-/- macrophages, ATG5 knockdown, IL-1β ELISA, inflammasome assembly assays Biochemical and biophysical research communications Medium 24971542
2014 End-binding protein 1 (EB1) is required for AIM2 inflammasome activation and links AIM2 inflammasomes to autophagy-dependent IL-1β secretion; AIM2 inflammasomes colocalize with microtubule organizing centers and autophagosomes; 5'-AMP activated protein kinase regulates EB1-mediated autophagy-based inflammasome-induced secretion. EB1 depletion, live-cell imaging (colocalization with MTOCs and autophagosomes), autophagy flux assays, IL-1β secretion assays, LC3-dependent secretion assays The Journal of biological chemistry Medium 25164813
2021 AIM2 has an inflammasome-independent, T cell-intrinsic role in regulatory T (Treg) cells: AIM2 interacts with the RACK1-PP2A phosphatase complex to restrain AKT phosphorylation, attenuating mTOR and MYC signaling and glycolysis while promoting oxidative phosphorylation, thereby enhancing Treg cell stability. T cell-conditional AIM2 knockout, RNA sequencing, biochemical/metabolic analyses, Co-IP (AIM2-RACK1-PP2A complex), lineage-tracing, AKT phosphorylation assays Nature High 33505023
2021 AIM2 forms a large multi-protein complex (PANoptosome) with pyrin and ZBP1, along with ASC, caspase-1, caspase-8, RIPK3, RIPK1, and FADD, to drive PANoptosis (simultaneous apoptosis, necroptosis, and pyroptosis) and host protection during HSV-1 and Francisella novicida infection. Co-immunoprecipitation of multi-protein complex, genetic knockouts (Aim2-/-, ZBP1-/-, Pyrin-/-), cell death assays (pyroptosis, apoptosis, necroptosis), in vivo infection models Nature High 34471287
2021 TRIM11 promotes selective autophagic degradation of AIM2 in CD4+ T cells by inducing AIM2 ubiquitination and binding to p62, thereby negatively regulating Treg cell differentiation in an AIM2-dependent manner. Co-immunoprecipitation (TRIM11-AIM2 and p62 interaction), ubiquitination assays, TRIM11 knockdown/overexpression in CD4+ T cells, Treg differentiation assays Cell reports Medium 37804507
2021 USP21 deubiquitinase binds to AIM2 upon DNA stimulation and deubiquitinates it, increasing its protein stability and preventing proteasomal degradation; additionally, USP21-mediated deubiquitination is required for AIM2-ASC complex formation (inflammasome assembly) but does not affect AIM2's DNA-binding ability. Co-immunoprecipitation, deubiquitination assays, USP21 depletion, proteasome inhibition, DNA-binding assays, AIM2-ASC complex assembly assays Journal of immunology High 34470856
2023 AIM2 preferentially binds dsDNA over ssDNA, dsRNA, ssRNA, or DNA:RNA hybrids in a duplex length-dependent manner; AIM2 oligomers assembled on non-dsDNA substrates display less ordered filamentous structures and fail to induce downstream ASC polymerization, establishing that filament assembly is the mechanistic basis for AIM2's dsDNA specificity. In vitro nucleic acid binding assays, cryo-EM/electron microscopy of filament structures, ASC polymerization assays with various nucleic acid substrates Nucleic acids research High 36864667
2017 AIM2 reviews detail that the HIN200 domain binds dsDNA while the PYD domain nucleates ASC PYD filament formation; structural studies (X-ray crystallography and cryo-EM) reveal that AIM2 inflammasome assembly proceeds via nucleated polymerization of helical filaments from AIM2 through ASC to caspase-1. X-ray crystallography, cryo-EM structural determination of AIM2-ASC-caspase-1 complex and filament intermediates Journal of structural biology High 28813641
2020 AIM2 promotes NSCLC cell growth independently of inflammasome activation by colocalizing with mitochondria; AIM2 knockdown leads to enhanced mitochondrial fusion via MFN2 upregulation, decreased ROS production, and inactivation of the MAPK/ERK signaling pathway. AIM2 knockdown in NSCLC cells, mitochondrial colocalization imaging, MFN2 expression analysis, ROS measurement, ERK phosphorylation assays, in vivo xenograft Oncogene Medium 32005973
2020 AIM2 inflammasome contributes to normal neurodevelopment through gasdermin-D-mediated pyroptosis (not IL-1/IL-18); AIM2 activation purges genetically compromised CNS cells during neurodevelopment, as AIM2-deficient mice show decreased neural cell death in response to DNA-damaging agents, excess accumulation of DNA damage in neurons, and increased neuron incorporation into the adult brain. Aim2-/- mice, gasdermin-D-/- mice, DNA damage-inducing agents, neural cell death quantification, behavioral assays (anxiety), BrdU neuron incorporation Nature High 32350463
2015 AIM2 drives joint inflammation in a self-DNA (DNase II-deficient) model of polyarthritis; Aim2-deficient arthritis-prone mice display strongly decreased joint inflammation, reduced caspase-1 activation, and reduced pro-inflammatory cytokine production in diseased joints, establishing tissue-specific AIM2 sensor function for endogenous DNA. Aim2-/- crossed to DNase II-/- mice, caspase-1 activation assays, cytokine measurement in joints, histopathology PloS one Medium 26114879
2016 AIM2 competes with STING for cytosolic M. bovis DNA binding, thereby inhibiting STING-TBK1-dependent autophagy activation and IFN-β secretion in Mycobacterium-infected macrophages. AIM2-knockdown macrophages, STING pathway readouts (IFN-β secretion, TBK1 activation), autophagy flux assays, M. bovis infection model Oncotarget Medium 27409673
2021 AIM2 is activated in blood monocytes infected with SARS-CoV-2 (via antibody-opsonized virus and Fc receptor CD16 uptake); abortive SARS-CoV-2 replication produces dsDNA that activates both NLRP3 and AIM2 inflammasomes, leading to caspase-1 and GSDMD activation and pyroptosis of monocytes. SARS-CoV-2-infected monocytes from COVID-19 patients, dsRNA/subgenomic RNA detection, caspase-1 and GSDMD activation assays, inflammasome genetic KO studies, lung macrophage autopsy Research squarepreprint Medium 34401873
2021 AIM2 in Treg cells attenuates AKT phosphorylation, mTOR and MYC signaling, and glycolysis via interaction with the RACK1-PP2A phosphatase complex; TRIM11 promotes AIM2 degradation via p62-mediated selective autophagy in CD4+ T cells, reducing Treg cell stability and promoting autoimmune disease. TRIM11/AIM2 interaction confirmed by Co-IP; ubiquitination assays, Treg differentiation assays, EAE mouse model Cell reports Medium 37804507
2024 EIF2AK2 directly targets and positively regulates AIM2 protein expression (confirmed by Co-IP); EIF2AK2-induced AIM2 upregulation drives PANoptosis in kidney tubular cells during septic AKI. Co-immunoprecipitation (EIF2AK2-AIM2 interaction), AIM2 knockdown in LPS-stimulated HK-2 cells, CLP mouse model, Western blot, LDH assay Renal failure Medium 39311631
2023 Pristimerin enhances K63-linked ubiquitin chains of PYCARD/ASC at K158/161 by binding USP50 deubiquitinase at Cys53 (via Michael-acceptor mechanism) and blocking USP50-mediated cleavage of K63-linked ubiquitin chains; this promotes SQSTM1/p62-mediated autophagic degradation of the AIM2-PYCARD/ASC complex. Drug affinity responsive target stability (DARTS), Co-IP, ubiquitination assays with K158/161 mutagenesis, site-directed mutagenesis of USP50 Cys53, p62 interaction assays, autophagy flux assays Autophagy High 37647255
2023 NLRP3 inhibits AIM2 inflammasome-mediated uveitis by regulating the p-SIK1/SREBF1 pathway: NLRP3 deficiency downregulates p-SIK1 and upregulates SREBF1, which binds to the Aim2 promoter to drive Aim2 transcription and AIM2-mediated pyroptosis. Nlrp3-/- mice, RNA sequencing, chromatin immunoprecipitation-PCR (SREBF1 binding to Aim2 promoter), Aim2-/- mice, SREBF1 RNA silencing, NLRP3 overexpression Arthritis & rheumatology High 36529965
2021 DROSHA ribonuclease III promotes AIM2 inflammasome activation; DROSHA deficiency suppresses AIM2-dependent caspase-1 activation and IL-1β/IL-18 secretion; DROSHA-processed miRNAs promote ASC speck formation required for AIM2 inflammasome activation. DROSHA-/- primary alveolar macrophages and BMDMs, caspase-1 activation assays, ASC speck formation imaging, IL-1β/IL-18 ELISA, miRNA transduction Cells Medium 31434287
2021 AIM2 and IFI16 (ALRs) bind neutrophil extracellular traps (NETs) both in vitro and in SLE renal tissues; ALR binding to NETs causes them to resist degradation by DNase I, suggesting a mechanism for sustained innate immune signaling. Immunoprecipitation, immunofluorescence colocalization, DNase protection assays, confocal microscopy of SLE renal tissue eLife Medium 35608258
2021 Nuclear AIM2-like receptors (ALRs) function as inhibitors of DNA repair by binding to and interfering with chromatin decompaction required for DNA repair, thereby accelerating genome destabilization, micronuclei generation, and cell death; this function is uncoupled from their inflammasome/innate immune role. ALR-knockout mice (irradiation resistance phenotype), chromatin binding assays, DNA repair assays, micronuclei quantification, cell death assays Advanced science Medium 34658166
2021 In gastric cancer, STAT3 (activated by IL-11) upregulates AIM2 expression in tumor epithelium; AIM2 physically interacts with microtubule-associated end-binding protein 1 (EB1) to promote epithelial cell migration and tumourigenesis independently of inflammasome activation. AIM2 genetic targeting in gp130F/F mouse model, AIM2-EB1 Co-IP in vivo and in vitro, xenograft models, inflammasome-independent functional assays, STAT3 reporter assays Gut High 34489308
2023 AIM2 promotes FOXO3a phosphorylation and proteasome-mediated degradation in renal cell carcinoma, thereby reducing FOXO3a transcriptional activity on ACSL4 and inhibiting ferroptosis, independent of inflammasome activation. AIM2 knockdown/overexpression in RCC cells, FOXO3a phosphorylation and ubiquitination assays, ACSL4 expression analysis, ferroptosis markers, in vivo xenograft International journal of biological sciences Medium 36923928

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 2105 19158675
2021 AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence. Nature 590 34471287
2016 PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation. Nature communications 451 27779186
2013 AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC. Cell death and differentiation 434 23645208
2021 The AIM2 inflammasome exacerbates atherosclerosis in clonal haematopoiesis. Nature 391 33731931
2017 Oxysterol Restraint of Cholesterol Synthesis Prevents AIM2 Inflammasome Activation. Cell 289 29033131
2018 The AIM2 inflammasome: Sensor of pathogens and cellular perturbations. Immunological reviews 285 29247998
2015 Inflammasome-independent role of AIM2 in suppressing colon tumorigenesis via DNA-PK and Akt. Nature medicine 248 26107252
2019 Role of AIM2 inflammasome in inflammatory diseases, cancer and infection. European journal of immunology 227 31372985
2020 AIM2 inflammasome surveillance of DNA damage shapes neurodevelopment. Nature 188 32350463
2013 Activation of NLRP3 and AIM2 inflammasomes by Porphyromonas gingivalis infection. Infection and immunity 188 24126516
2020 AIM2 in health and disease: Inflammasome and beyond. Immunological reviews 185 32713036
2017 AIM2 inflammasome activation and regulation: A structural perspective. Journal of structural biology 178 28813641
2021 Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome. Nature communications 173 34006824
2016 TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p62-Dependent Selective Autophagy. Cell reports 146 27498865
2021 AIM2 in regulatory T cells restrains autoimmune diseases. Nature 137 33505023
2021 Structure, Activation and Regulation of NLRP3 and AIM2 Inflammasomes. International journal of molecular sciences 135 33467177
2018 Macrophage Uptake of Necrotic Cell DNA Activates the AIM2 Inflammasome to Regulate a Proinflammatory Phenotype in CKD. Journal of the American Society of Nephrology : JASN 132 29439156
2016 Antagonism of the STING Pathway via Activation of the AIM2 Inflammasome by Intracellular DNA. Journal of immunology (Baltimore, Md. : 1950) 130 26927800
2023 Integrated NLRP3, AIM2, NLRC4, Pyrin inflammasome activation and assembly drive PANoptosis. Cellular & molecular immunology 122 38008850
2022 Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma. The Journal of clinical investigation 115 35199647
2020 Inhibition of AIM2 inflammasome activation alleviates GSDMD-induced pyroptosis in early brain injury after subarachnoid haemorrhage. Cell death & disease 109 32001670
2016 Loss of AIM2 expression promotes hepatocarcinoma progression through activation of mTOR-S6K1 pathway. Oncotarget 105 27167192
2022 Overexpression of NAG-1/GDF15 prevents hepatic steatosis through inhibiting oxidative stress-mediated dsDNA release and AIM2 inflammasome activation. Redox biology 103 35504134
2017 AIM2 Inflammasome Is Critical for Influenza-Induced Lung Injury and Mortality. Journal of immunology (Baltimore, Md. : 1950) 99 28424239
2017 HBx-mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis. Molecular oncology 82 28580773
2023 Immune regulator IRF1 contributes to ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosome activation and inflammatory cell death (PANoptosis). The Journal of biological chemistry 81 37557956
2015 AIM2 Drives Joint Inflammation in a Self-DNA Triggered Model of Chronic Polyarthritis. PloS one 79 26114879
2021 AIM2 deficiency in B cells ameliorates systemic lupus erythematosus by regulating Blimp-1-Bcl-6 axis-mediated B-cell differentiation. Signal transduction and targeted therapy 78 34521812
2021 The AIM2 and NLRP3 inflammasomes trigger IL-1-mediated antitumor effects during radiation. Science immunology 77 33963060
2020 Immunobiology and structural biology of AIM2 inflammasome. Molecular aspects of medicine 76 32660715
2020 AIM2 promotes the development of non-small cell lung cancer by modulating mitochondrial dynamics. Oncogene 75 32005973
2019 AIM2 Inflammasome Assembly and Signaling. Advances in experimental medicine and biology 75 31628655
2021 The Role of NLRP1, NLRP3, and AIM2 Inflammasomes in Psoriasis: Review. International journal of molecular sciences 69 34072753
2022 The AIM2 inflammasome: A novel biomarker and target in cardiovascular disease. Pharmacological research 65 36332811
2021 Mitochondrial DNA enables AIM2 inflammasome activation and hepatocyte pyroptosis in nonalcoholic fatty liver disease. American journal of physiology. Gastrointestinal and liver physiology 64 33728991
2021 SARS-CoV-2 infects blood monocytes to activate NLRP3 and AIM2 inflammasomes, pyroptosis and cytokine release. Research square 61 34401873
2021 AIM2 regulates anti-tumor immunity and is a viable therapeutic target for melanoma. The Journal of experimental medicine 59 34325468
2013 Participation of c-FLIP in NLRP3 and AIM2 inflammasome activation. Cell death and differentiation 59 24270411
2017 AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA. mBio 57 28679751
2014 HMGB1-DNA complex-induced autophagy limits AIM2 inflammasome activation through RAGE. Biochemical and biophysical research communications 56 24971542
2016 The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection. Seminars in immunopathology 55 27405866
2023 AIM2 promotes renal cell carcinoma progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated ferroptosis. International journal of biological sciences 54 36923928
2017 Methylene blue inhibits NLRP3, NLRC4, AIM2, and non-canonical inflammasome activation. Scientific reports 51 28963531
2022 The DNA sensors AIM2 and IFI16 are SLE autoantigens that bind neutrophil extracellular traps. eLife 50 35608258
2014 Identification of Aim2 as a sensor for DNA vaccines. Journal of immunology (Baltimore, Md. : 1950) 50 25488991
2017 Interaction between HCMV pUL83 and human AIM2 disrupts the activation of the AIM2 inflammasome. Virology journal 49 28219398
2021 Blockade of AIM2 inflammasome or α1-AR ameliorates IL-1β release and macrophage-mediated immunosuppression induced by CAR-T treatment. Journal for immunotherapy of cancer 47 33414262
2021 The complex role of AIM2 in autoimmune diseases and cancers. Immunity, inflammation and disease 43 34014039
2014 The microtubule-associated protein EB1 links AIM2 inflammasomes with autophagy-dependent secretion. The Journal of biological chemistry 42 25164813
2020 Chronic cerebral hypoperfusion activates AIM2 and NLRP3 inflammasome. Brain research 40 32171704
2018 Increased Levels of AIM2 and Circulating Mitochondrial DNA in Type 2 Diabetes. Iranian journal of immunology : IJI 40 29947343
2021 Downregulating expression of OPTN elevates neuroinflammation via AIM2 inflammasome- and RIPK1-activating mechanisms in APP/PS1 transgenic mice. Journal of neuroinflammation 39 34861878
2017 AIM2 regulates viability and apoptosis in human colorectal cancer cells via the PI3K/Akt pathway. OncoTargets and therapy 38 28243117
2024 Neutrophil extracellular traps promote acetaminophen-induced acute liver injury in mice via AIM2. Acta pharmacologica Sinica 37 38589685
2017 Human cytomegalovirus triggers the assembly of AIM2 inflammasome in THP-1-derived macrophages. Journal of medical virology 36 28480966
2020 The Emerging Relevance of AIM2 in Liver Disease. International journal of molecular sciences 35 32906750
2018 AIM2 regulates vascular smooth muscle cell migration in atherosclerosis. Biochemical and biophysical research communications 35 29448104
2021 STAT3-mediated upregulation of the AIM2 DNA sensor links innate immunity with cell migration to promote epithelial tumourigenesis. Gut 33 34489308
2023 Hematopoietic NLRP3 and AIM2 Inflammasomes Promote Diabetes-Accelerated Atherosclerosis, but Increased Necrosis Is Independent of Pyroptosis. Diabetes 32 37083999
2021 The emerging roles of absent in melanoma 2 (AIM2) inflammasome in central nervous system disorders. Neurochemistry international 32 34284076
2023 NLRP3 Attenuates Intraocular Inflammation by Inhibiting AIM2-Mediated Pyroptosis Through the Phosphorylated Salt-Inducible Kinase 1/Sterol Regulatory Element Binding Transcription Factor 1 Pathway. Arthritis & rheumatology (Hoboken, N.J.) 31 36529965
2023 Pristimerin suppresses AIM2 inflammasome by modulating AIM2-PYCARD/ASC stability via selective autophagy to alleviate tendinopathy. Autophagy 30 37647255
2020 Expression of AIM2 in Rheumatoid Arthritis and Its Role on Fibroblast-Like Synoviocytes. Mediators of inflammation 30 33162829
2019 Expression of inflammasomes NLRP1, NLRP3 and AIM2 in different pathologic classification of lupus nephritis. Clinical and experimental rheumatology 30 31694740
2024 Ginsenoside Rg1 alleviates chronic inflammation-induced neuronal ferroptosis and cognitive impairments via regulation of AIM2 - Nrf2 signaling pathway. Journal of ethnopharmacology 29 38641079
2018 Differential Activation of NLRP3, AIM2, and IFI16 Inflammasomes in Humans with Acute and Chronic Hepatitis B. Viral immunology 29 30222506
2022 Neutrophil extracellular traps promote keratinocyte inflammation via AIM2 inflammasome and AIM2-XIAP in psoriasis. Experimental dermatology 28 36401800
2022 Re-Du-Ning injection ameliorates radiation-induced pneumonitis and fibrosis by inhibiting AIM2 inflammasome and epithelial-mesenchymal transition. Phytomedicine : international journal of phytotherapy and phytopharmacology 27 35665679
2020 AIM2 inhibits colorectal cancer cell proliferation and migration through suppression of Gli1. Aging 27 33291082
2017 Maturation-dependent expression of AIM2 in human B-cells. PloS one 27 28809949
2023 Exercise alleviates neovascular age-related macular degeneration by inhibiting AIM2 inflammasome in myeloid cells. Metabolism: clinical and experimental 26 37150437
2022 AIM2 upregulation promotes metastatic progression and PD-L1 expression in lung adenocarcinoma. Cancer science 26 36104978
2021 Diabetes induces macrophage dysfunction through cytoplasmic dsDNA/AIM2 associated pyroptosis. Journal of leukocyte biology 26 34085308
2015 Deficient NLRP3 and AIM2 Inflammasome Function in Autoimmune NZB Mice. Journal of immunology (Baltimore, Md. : 1950) 26 26116505
2024 New insights into nucleic acid sensor AIM2: The potential benefit in targeted therapy for cancer. Pharmacological research 24 38272334
2023 Baicalein Suppresses NLRP3 and AIM2 Inflammasome-Mediated Pyroptosis in Macrophages Infected by Mycobacterium tuberculosis via Induced Autophagy. Microbiology spectrum 24 37125940
2019 AIM2 deletion promotes neuroplasticity and spatial memory of mice. Brain research bulletin 24 31301379
2023 AIM2 and Psoriasis. Frontiers in immunology 23 36742336
2024 EIF2AK2 protein targeted activation of AIM2-mediated PANoptosis promotes sepsis-induced acute kidney injury. Renal failure 22 39311631
2021 USP21 Deubiquitinase Regulates AIM2 Inflammasome Activation. Journal of immunology (Baltimore, Md. : 1950) 22 34470856
2019 DROSHA-Dependent AIM2 Inflammasome Activation Contributes to Lung Inflammation during Idiopathic Pulmonary Fibrosis. Cells 22 31434287
2024 Neutrophil extracellular traps facilitate liver inflammation/fibrosis progression by entering macrophages and triggering AIM2 inflammasome-dependent pyroptosis. Cell communication and signaling : CCS 21 39568027
2022 Cross-talk between IL-6 trans-signaling and AIM2 inflammasome/IL-1β axes bridge innate immunity and epithelial apoptosis to promote emphysema. Proceedings of the National Academy of Sciences of the United States of America 21 36037355
2021 Nuclear AIM2-Like Receptors Drive Genotoxic Tissue Injury by Inhibiting DNA Repair. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 21 34658166
2016 AIM2 inhibits autophagy and IFN-β production during M. bovis infection. Oncotarget 21 27409673
2013 Expression of AIM2 is high and correlated with inflammation in hepatitis B virus associated glomerulonephritis. Journal of inflammation (London, England) 21 24325587
2022 AIM2-inflammasome role in systemic lupus erythematous and rheumatoid arthritis. Autoimmunity 19 35880661
2022 Absent in melanoma 2 (AIM2) in rheumatoid arthritis: novel molecular insights and implications. Cellular & molecular biology letters 19 36476420
2020 Fructose-arginine, a non-saponin molecule of Korean Red Ginseng, attenuates AIM2 inflammasome activation. Journal of ginseng research 19 33192124
2024 Bruceine A alleviates alcoholic liver disease by inhibiting AIM2 inflammasome activation via activating FXR. Phytomedicine : international journal of phytotherapy and phytopharmacology 18 38763006
2023 Genomic DNA activates the AIM2 inflammasome and STING pathways to induce inflammation in lacrimal gland myoepithelial cells. The ocular surface 18 37769964
2025 The histone lactylation of AIM2 influences the suppression of ferroptosis by ACSL4 through STAT5B and promotes the progression of lung cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 39792364
2023 Overexpressed CD44 is associated with B-cell activation via the HA-CD44-AIM2 pathway in lupus B cells. Clinical immunology (Orlando, Fla.) 16 37499961
2023 TRIM11 attenuates Treg cell differentiation by p62-selective autophagic degradation of AIM2. Cell reports 16 37804507
2022 Absent in Melanoma 2 (AIM2) Regulates the Stability of Regulatory T Cells. International journal of molecular sciences 16 35216346
2024 Microglial mitochondrial DNA release contributes to neuroinflammation after intracerebral hemorrhage through activating AIM2 inflammasome. Experimental neurology 15 39278588
2023 Filament assembly underpins the double-stranded DNA specificity of AIM2-like receptors. Nucleic acids research 15 36864667
2023 The role of AIM2 in human hepatocellular carcinoma and its clinical significance. Pathology, research and practice 15 37060822
2019 Expression and activity of AIM2-inflammasome in rheumatoid arthritis patients. Immunobiology 15 31836304