Affinage

CARD8

Caspase recruitment domain-containing protein 8 · UniProt Q9Y2G2

Length
537 aa
Mass
60.7 kDa
Annotated
2026-04-28
100 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CARD8 is an innate immune sensor and inflammasome-forming protein that integrates danger signals—including viral protease activity, DPP8/9 inhibition, and protein folding stress—to activate caspase-1-dependent pyroptosis. CARD8 undergoes constitutive autoproteolysis at a conserved SF/S motif within its FIIND (ZU5-UPA) domain, generating non-covalently associated N-terminal (NT) and C-terminal (CT) fragments; the disordered NT region is degraded by the ubiquitin-independent 20S proteasome upon stress, while DPP9 physically sequesters released CT fragments, establishing a two-signal requirement for inflammasome assembly in which both NT degradation and DPP9 sequestration disruption must coincide to allow CT (UPA-CARD) oligomerization into helical filaments that directly recruit and activate caspase-1 without ASC (PMID:22087307, PMID:35580636, PMID:36649711, PMID:33420033). CARD8 functions as a broad viral protease tripwire: HIV-1, SARS-CoV-2, and enteroviral proteases cleave a rapidly evolving N-terminal region, triggering proteasome-dependent inflammasome activation and pyroptosis of infected cells—a mechanism that in vivo contributes to HIV-induced CD4+ T cell depletion in quiescent lymphocytes (PMID:33542150, PMID:37289745, PMID:36129453, PMID:38428396). Independently of its inflammasome role, CARD8 exerts anti-inflammatory functions by binding NEMO to suppress NF-κB signaling, interacting with NLRP3 to prevent its deubiquitination and dephosphorylation, and inhibiting NOD2-mediated nodosome assembly (PMID:11551959, PMID:29408806, PMID:20385562).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 High

    The first functional studies established that CARD8 is a potent suppressor of NF-κB activation by showing it co-immunoprecipitates with the IKK regulatory subunit NEMO and blocks signaling downstream of multiple NF-κB-activating stimuli, defining its anti-inflammatory role.

    Evidence Co-immunoprecipitation and NF-κB reporter assays with overexpression of multiple pathway activators in cell lines

    PMID:11408476 PMID:11551959

    Open questions at the time
    • Endogenous stoichiometry of CARD8-NEMO interaction unknown
    • No structural basis for NEMO binding
    • In vivo relevance of NF-κB suppression not tested
  2. 2002 High

    CARD8 was shown to physically interact with caspase-1 via its CARD domain and suppress caspase-1-dependent IL-1β processing, establishing it as a negative regulator of inflammasome output in addition to NF-κB.

    Evidence Co-immunoprecipitation and IL-1β ELISA in THP-1 monocytic cells with overexpression/knockdown

    PMID:11821383

    Open questions at the time
    • Mechanism by which CARD8 inhibits caspase-1 not resolved
    • Relationship between caspase-1 inhibition and NF-κB inhibition unclear
  3. 2010 High

    Discovery that CARD8 interacts with NOD2 and inhibits nodosome assembly expanded CARD8's role to suppression of bacterial peptidoglycan sensing pathways, showing it controls NOD2-mediated NF-κB signaling and intracellular bactericidal function.

    Evidence Co-immunoprecipitation, siRNA knockdown, NF-κB reporter assays, and Listeria killing assay in intestinal epithelial cells

    PMID:20385562

    Open questions at the time
    • Whether CARD8 regulation of NOD2 is direct or scaffold-mediated unknown
    • Physiological relevance in intestinal inflammation not demonstrated in vivo
  4. 2011 High

    Identification of FIIND domain autoproteolysis at a conserved SF/S motif revealed that CARD8 (like NLRP1) is post-translationally self-processed, fundamentally reframing its activation mechanism as requiring cleavage-generated fragments rather than simple conformational change.

    Evidence Site-directed mutagenesis of SF/S motif and flanking residues, biochemical cleavage assays, computational ZU5-UPA modeling

    PMID:22087307

    Open questions at the time
    • Functional consequence of autoproteolysis for inflammasome activation not yet tested
    • Crystal structure of FIIND not determined
  5. 2018 High

    A missense mutation (V44I) in the CARD8 T60 isoform that abolished NLRP3 binding and caused Crohn's disease established that CARD8 directly restrains NLRP3 inflammasome activation by preventing NLRP3 deubiquitination and dephosphorylation, linking CARD8 loss-of-function to human autoinflammatory disease.

    Evidence Whole exome sequencing, Co-IP, PTM analysis of NLRP3, dominant-negative oligomerization studies, patient monocyte IL-1β assays

    PMID:29408806

    Open questions at the time
    • Direct binding interface between CARD8 and NLRP3 not structurally resolved
    • Specific phosphatase/DUB regulated by CARD8 unknown
  6. 2019 High

    Reconstitution experiments demonstrated that DPP9 catalytic activity—not merely DPP9 protein binding—restrains CARD8 inflammasome activation, distinguishing the CARD8-DPP9 regulatory mechanism from the NLRP1-DPP9 interaction.

    Evidence DPP9 KO rescue with catalytic mutant, activity-based probes, MS proteomics in reconstituted inflammasome assays

    PMID:31525884

    Open questions at the time
    • Identity of DPP9 substrate(s) relevant to CARD8 restraint unknown
    • Physical interface for DPP9-CARD8 not resolved
  7. 2020 High

    Genetic dissection revealed that DPP8/9 inhibition triggers proteasomal degradation of the disordered CARD8 N-terminal region, freeing the C-terminal UPA-CARD fragment to activate caspase-1 and induce pyroptosis—establishing the 'functional degradation' model of CARD8 inflammasome activation.

    Evidence CRISPR KO, domain deletion mutants, proteasome inhibitors, caspase-1 activity and cell death assays in monocytic cells and primary T cells

    PMID:32796818 PMID:32840892 PMID:33053349

    Open questions at the time
    • Mechanism by which DPP8/9 inhibition triggers NT degradation not identified
    • Basis for resistance of activated T cells unknown
  8. 2021 High

    Cryo-EM structures of the CARD8 CT assembly revealed that UPA oligomerization promotes CARD helical filament formation, and that CARD8-CARD directly recruits caspase-1 using distinct structural surfaces from NLRP1 (which recruits ASC), resolving the signaling architecture of the CARD8 inflammasome.

    Evidence Cryo-EM at 3.7 Å resolution, recombinant protein reconstitution, ASC speck and oligomerization assays

    PMID:33420028 PMID:33420033

    Open questions at the time
    • Full-length CARD8 structure not resolved
    • Transition from DPP9-sequestered to oligomerized state not structurally captured
  9. 2021 High

    Discovery that HIV-1 protease cleaves the CARD8 N-terminus to trigger inflammasome-mediated pyroptosis of infected CD4+ T cells established CARD8 as a pathogen sensor that detects intracellular viral protease activity as a danger signal.

    Evidence HIV protease activation system, CARD8 KO in CD4+ T cells, pyroptosis assays, patient latent HIV reactivation model

    PMID:33542150

    Open questions at the time
    • Precise cleavage site not mapped in this study
    • In vivo significance for HIV pathogenesis not yet addressed
  10. 2022 High

    Mechanistic work showed the 20S proteasome (ubiquitin-independent) specifically degrades the CARD8 NT fragment, and that protein folding stress accelerates NT degradation but requires simultaneous disruption of DPP9-mediated CT sequestration for inflammasome assembly—establishing a two-signal activation model.

    Evidence 20S-specific inhibitors/activators, domain-specific degradation assays, DPP9 binding assays, inflammasome formation assays

    PMID:35580636 PMID:36649711

    Open questions at the time
    • Structural basis for 20S recognition of CARD8 NT not determined
    • Whether other E3-independent proteasome substrates use similar mechanism unknown
  11. 2022 High

    Enterovirus (CVB3) 2A and 3C proteases were shown to cleave CARD8 at G38 to activate inflammasome-dependent pyroptosis in endothelial cells and cardiomyocytes, extending the viral protease tripwire model beyond retroviruses to picornaviruses.

    Evidence CARD8 KO via CRISPR, cleavage site mapping, proteasome inhibition, CVB3 infection model in endothelial cells and cardiomyocytes

    PMID:36129453

    Open questions at the time
    • Relative contribution of 2A vs 3C protease in vivo not resolved
    • Whether CARD8 activation is protective or pathogenic during myocarditis unclear
  12. 2023 High

    SARS-CoV-2 3CLpro was identified as a CARD8 activator, and natural human SNPs were found to shift CARD8 specificity between coronavirus and picornavirus proteases, revealing that the CARD8 N-terminal tripwire is a rapidly evolving pathogen sensor with intraspecies functional variation.

    Evidence CARD8 KO cells, viral protease expression, SARS-CoV-2 infection model, natural polymorphism analysis across human populations

    PMID:37289745 PMID:37417868

    Open questions at the time
    • How balancing selection shapes CARD8 allele frequency not modeled
    • Structural basis for protease specificity switching by single SNPs unknown
  13. 2024 High

    In vivo CARD8 KO humanized mice demonstrated that CARD8-mediated pyroptosis of quiescent CD4+ T cells driven by incoming virion-packaged HIV protease contributes to CD4+ T cell depletion, and natural SIV hosts carrying CARD8 loss-of-function mutations avoid pathogenic T cell depletion, establishing CARD8 as a determinant of HIV/SIV pathogenesis.

    Evidence CARD8-deficient humanized mouse model, incoming virion protease activation assay, CD4+ depletion tracking, CARD8 sequencing in natural SIV host species

    PMID:38428396

    Open questions at the time
    • Whether CARD8 contributes to human elite controller or long-term nonprogressor phenotype unknown
    • Therapeutic modulation of CARD8 in HIV not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis of the DPP9-CARD8 sequestration complex, the identity of DPP9 substrates whose accumulation triggers CARD8 NT degradation, the mechanism by which T cell activation abolishes CARD8 inflammasome competence, and whether CARD8's anti-inflammatory functions (NLRP3/NOD2/NF-κB suppression) and pro-inflammatory inflammasome functions are coordinated or context-dependent in vivo.
  • No structure of DPP9-CARD8 complex
  • DPP9 substrate identity upstream of CARD8 NT degradation unknown
  • Mechanism of T cell activation-induced CARD8 silencing not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140299 molecular sensor activity 4 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005829 cytosol 3
Pathway
R-HSA-168256 Immune System 7 R-HSA-5357801 Programmed Cell Death 6 R-HSA-162582 Signal Transduction 3
Partners
CASP1DPP9FADDGSDMDIKBKGNLRP3NOD2
Complex memberships
CARD8 inflammasomeDPP9-CARD8 inhibitory complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 CARD8 physically interacts with caspase-1 via its CARD domain and negatively regulates caspase-1-dependent IL-1β generation in THP-1 monocytic cells; CARD8 also binds ICEBERG and pseudo-ICE (other caspase-1 CARD-binding proteins). Additionally, CARD8 negatively regulates NF-κB activation induced by TNF-α stimulation and by ectopically expressed RICK, and stable CARD8 expression sensitizes U937/THP-1 cells to differentiation-induced apoptosis. Co-immunoprecipitation, overexpression in THP-1/U937 cells with IL-1β ELISA readout, NF-κB reporter assays The Journal of biological chemistry High 11821383
2001 CARDINAL (CARD8) potently suppresses NF-κB activation downstream of multiple stimuli (TRAIL-R1, TRAIL-R2, RIP, RICK, Bcl10, TRADD, IL-1, TNF) and co-immunoprecipitates with IKKγ (NEMO), the regulatory subunit of the IκB kinase complex, providing a molecular basis for its NF-κB inhibitory function. Co-immunoprecipitation, NF-κB reporter assays with overexpression of multiple upstream activators The Journal of biological chemistry High 11551959
2001 TUCAN (CARD8) CARD domain selectively binds itself and procaspase-9, interferes with Apaf1 binding to procaspase-9, and suppresses caspase activation induced by Apaf1/caspase-9-dependent stimuli (Bax, VP16, staurosporine) but not by Apaf1/caspase-9-independent stimuli (Fas, granzyme B). Pulldown/binding assays, stable transfection with caspase activity assays, apoptosis assays The Journal of biological chemistry Medium 11408476
2002 TUCAN/CARDINAL associates with DRAL (a p53-responsive apoptosis-inducing protein), and while CARD8 suppresses NF-κB activity, DRAL enhances it, suggesting they participate in a regulatory mechanism coordinating NF-κB-controlled cellular responses. Co-immunoprecipitation, NF-κB reporter assays FEBS letters Medium 12067710
2011 CARD8 and NLRP1 undergo autoproteolytic cleavage at a conserved SF/S motif within the FIIND domain. Bioinformatics and computational modeling revealed structural similarity between FIIND and the ZU5-UPA domain of PIDD. Site-directed mutagenesis showed the second serine of the SF/S motif is required for autoproteolysis; conserved glutamic acid and histidine residues near the cleavage site regulate autoprocessing efficiency. Site-directed mutagenesis, biochemical cleavage assays, bioinformatics/computational modeling PloS one High 22087307
2010 CARD8 physically interacts with NOD2 and inhibits nodosome assembly and subsequent NOD2-mediated signaling upon muramyl-dipeptide stimulation in intestinal epithelial cells; CARD8 also inhibits the direct bactericidal effect of NOD2 against intracellular Listeria monocytogenes. Co-immunoprecipitation, siRNA knockdown, NF-κB reporter assays, intracellular bacterial killing assay The Journal of biological chemistry High 20385562
2017 A frameshift variant in CARD8 (CARD8-FS) produces a truncated protein lacking FIIND and CARD domains that loses the ability to interact with the NOD domain of NLRP3, linking CARD8's NLRP3-binding function to autoinflammation regulation in PFAPA syndrome patients. Next-generation sequencing, co-immunoprecipitation (CARD8 vs. NLRP3), functional comparison of wild-type vs. truncated protein Journal of immunology Medium 28137891
2018 A missense mutation (V44I) in the T60 isoform of CARD8 prevents binding to NLRP3 and inhibition of NLRP3 oligomerization, leading to NLRP3 inflammasome hyperactivation and Crohn's disease. The mutant T60 CARD8 exerts a dominant-negative effect by forming oligomers with wild-type T60 or T48 CARD8 that impede their NLRP3 binding. Wild-type CARD8 prevents NLRP3 deubiquitination and serine dephosphorylation. Whole exome sequencing, immunoblot, Co-immunoprecipitation, monocyte IL-1β stimulation, inflammasome activation assays The Journal of clinical investigation High 29408806
2019 DPP9's catalytic enzymatic activity—not its direct protein binding to CARD8—restrains the CARD8 inflammasome. Unlike the DPP9-NLRP1 interaction, the DPP9-CARD8 protein interaction is not disrupted by DPP9 inhibitors or CARD8 autoproteolysis-blocking mutations; wild-type but not catalytically inactive DPP9 rescues CARD8-mediated cell death in DPP9 KO cells. Activity-based probes, reconstituted inflammasome assays, mass spectrometry proteomics, DPP9 KO cells with rescue experiments ACS chemical biology High 31525884
2020 DPP8/9 inhibition activates a proteasomal degradation pathway targeting the disordered N-terminal region (~160 amino acids) of CARD8 for destruction, freeing the C-terminal fragment (UPA-CARD) from autoinhibition to activate caspase-1 and induce pyroptosis. The disordered N-terminal region is the critical signal recognized by this degradation pathway. Genetic dissection (CRISPR KO), domain deletion mutants, proteasome inhibitors, cell death assays (LDH, PI staining), caspase-1 activity Cell reports High 33053349
2020 CARD8 inflammasome activation in primary human CD4+ and CD8+ T cells (resting but not activated) triggers pyroptosis via the CARD8-caspase-1-GSDMD axis in response to DPP8/9 inhibition; DPP9 is the relevant DPP restraining CARD8 in T cells. CRISPR/RNAi genetic dissection of pathway components in primary T cells, morphological and biochemical pyroptosis assays, DPP isoform-specific knockdown The EMBO journal High 32840892
2020 DPP8/9 inhibitors activate the CARD8 inflammasome (not NLRP1) to induce pyroptosis in resting human and rodent CD4+ and CD8+ T lymphocytes; activated T cells are completely resistant despite expressing CARD8 pathway components. Pharmacological inhibitors, genetic validation (CARD8 KO), pyroptosis assays in primary lymphocyte subsets Cell death & disease High 32796818
2021 CARD8 senses HIV-1 protease activity as an inflammasome trigger. Premature intracellular activation of viral protease triggered CARD8 inflammasome-mediated pyroptosis of HIV-1-infected cells. Protease activity (not other viral components) is the CARD8-sensed signal. HIV protease activation system, CARD8 KO/knockdown in CD4+ T cells, pyroptosis assays, patient latent HIV reactivation model Science High 33542150
2021 Cryo-EM structures of CARD8-CT assembly reveal that CARD8 CARD forms a central helical filament promoted by surrounding oligomerized UPA subdomains; UPA reduces the threshold for CARD8-CT filament formation and signaling. Structural analyses show CARD8-CT directly recruits caspase-1 (contrasting with NLRP1-CT which recruits ASC). CARD8 and NLRP1 use distinct CARD surfaces to achieve signaling specificity. Cryo-EM structure determination (3.7 Å), biochemical oligomerization assays, cellular speck formation assays Nature communications High 33420033
2021 Cryo-EM structures of NLRP1 and CARD8 FIINDUPA-CARD reveal distinct inflammasome architectures: NLRP1 forms a two-layered filament with CARD core surrounded by FIINDUPA, while CARD8 forms distinct oligomers. CARD8-CARD filaments enable direct caspase-1 recruitment without ASC, whereas NLRP1-CARD recruits ASC. NLRP1 and CARD8 discriminate between ASC and pro-caspase-1 through unique structural features. Cryo-EM structure determination (3.7 Å), recombinant protein reconstitution, ASC speck formation in cultured cells, in vitro oligomerization Nature communications High 33420028
2022 The core 20S proteasome (ubiquitin-independent) controls CARD8 inflammasome activation by degrading the disordered NT region. In unstressed cells, 20S proteasome degrades only the NT disordered region, leaving ZU5-UPA-CARD as an inflammasome inhibitor. In Val-boroPro-stressed cells, the entire NT fragment (including the folded ZU5 domain) is degraded, possibly due to ZU5 unfolding, freeing the CT fragment. Proteasome inhibitor experiments, 20S-specific activators/inhibitors, domain-specific degradation assays, cell death assays The Journal of biological chemistry High 35580636
2022 M24B aminopeptidase inhibitor CQ31 selectively activates CARD8 (not NLRP1) by inhibiting PEPD and XPNPEP1, leading to accumulation of proline-containing peptides that inhibit DPP8/9. These proline-containing peptides do not disrupt the DPP9-NLRP1 active-site interaction (unlike VbP), explaining CARD8 selectivity. Small molecule screening, biochemical aminopeptidase activity assays, CARD8/NLRP1 inflammasome activation assays, MS-based identification of accumulated peptides Nature chemical biology High 35165443
2022 CARD8 inflammasome is activated in human endothelial cells and cardiomyocytes by Enterovirus Coxsackievirus B3 (CVB3) 2A and 3C viral protease cleavage of CARD8 at p.G38 in a proteasome-dependent manner; CARD8 genetic deletion attenuates CVB3-induced pyroptosis, inflammation, and viral propagation in endothelial cells and cardiomyocytes. CARD8 KO (CRISPR), protease cleavage site mapping (p.G38), proteasome inhibition, CVB3 infection model, co-culture system The Journal of experimental medicine High 36129453
2023 Coronavirus 3CL protease (3CLpro), including SARS-CoV-2, cleaves a rapidly evolving region of human CARD8 to activate an inflammasome response; CARD8 is required for cell death and pro-inflammatory cytokine release during SARS-CoV-2 infection. A human SNP reduces CARD8 sensing of coronavirus 3CLpros but enables sensing of picornavirus 3C proteases (3Cpro), revealing CARD8 as a broad viral protease sensor with intraspecies variation. CARD8 KO cells, viral protease expression, cleavage assays, SARS-CoV-2 infection model, natural variation analysis PLoS biology High 37289745
2023 HIV-1 protease cleaves CARD8 at a specific site within a human-specific motif in the CARD8 N-terminus, inducing pyroptosis and pro-inflammatory cytokine release. CARD8 senses both de novo translated HIV-1 protease and packaged protease released from incoming virions. The HIV-1PR cleavage site arose after human-chimpanzee divergence; chimpanzee CARD8 does not recognize HIV or SIVcpz protease, though SIVcpz can cleave human CARD8. HIV protease cleavage mapping, CARD8 KO cells, acute infection model, evolutionary sequence analysis, site-specific mutagenesis eLife High 37417868
2023 Protein folding stress agents (aminopeptidase inhibitors, chaperone inhibitors, unfolded protein response inducers) accelerate CARD8 NT fragment degradation but alone do not trigger inflammasome formation because released CT fragments are physically sequestered by DPP9. Both DPP9 protein sequestration disruption and NT degradation must occur simultaneously to allow CT fragment oligomerization into inflammasomes. Pharmacological agents, biochemical fragment detection, DPP9 binding assays, inflammasome formation assays Cell reports High 36649711
2024 CARD8 inflammasome is activated immediately after HIV entry by viral protease encapsulated in incoming virions, causing rapid pyroptosis of quiescent CD4+ T cells without productive infection. T cell activation abolishes CARD8 function and increases permissiveness to infection. In humanized mice reconstituted with CARD8-deficient cells, CD4+ depletion is delayed despite high viremia. Natural SIV 'non-pathogenic host' species harbor loss-of-function CARD8 mutations. CARD8 KO humanized mice, incoming virion protease activation assay, CD4+ T cell depletion tracking, CARD8 sequencing in natural SIV hosts Cell High 38428396
2005 A novel 54 kDa TUCAN (CARD8) isoform (TUCAN-54) suppresses both caspase-8 and caspase-9 mediated apoptosis; TUCAN-54 physically associates with FADD (Fas-associated death domain protein), unlike the 48 kDa isoform, enabling it to inhibit Fas-induced cell death in addition to the mitochondrial apoptosis pathway. Stable transfection/siRNA knockdown, caspase activity assays, co-immunoprecipitation (TUCAN-54 vs FADD), cell death assays Cancer research Medium 16204039

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos. Blood 179 22859612
2021 Heme Oxgenase-1, a Cardinal Modulator of Regulated Cell Death and Inflammation. Cells 174 33671004
2011 CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain. PloS one 172 22087307
2002 CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis. The Journal of biological chemistry 150 11821383
2020 The NLRP1 and CARD8 inflammasomes. Immunological reviews 148 32558991
2009 Combined polymorphisms in genes encoding the inflammasome components NALP3 and CARD8 confer susceptibility to Crohn's disease in Swedish men. The American journal of gastroenterology 138 19319132
2021 CARD8 is an inflammasome sensor for HIV-1 protease activity. Science (New York, N.Y.) 131 33542150
2020 CARD8 inflammasome activation triggers pyroptosis in human T cells. The EMBO journal 131 32840892
2022 iPSC-based disease modeling and drug discovery in cardinal neurodegenerative disorders. Cell stem cell 125 35120619
2013 The zebrafish common cardinal veins develop by a novel mechanism: lumen ensheathment. Development (Cambridge, England) 114 23698350
2004 Van der Woude syndrome: a review. Cardinal signs, epidemiology, associated features, differential diagnosis, expressivity, genetic counselling and treatment. European journal of orthodontics 101 14994878
2001 CARDINAL, a novel caspase recruitment domain protein, is an inhibitor of multiple NF-kappa B activation pathways. The Journal of biological chemistry 100 11551959
2009 Skin disease: a cardinal feature of systemic sclerosis. Rheumatology (Oxford, England) 98 19487217
2001 TUCAN, an antiapoptotic caspase-associated recruitment domain family protein overexpressed in cancer. The Journal of biological chemistry 97 11408476
2011 Impaired GABA and glycine transmission triggers cardinal features of rapid eye movement sleep behavior disorder in mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 95 21562273
2011 Enhanced autophagy plays a cardinal role in mitochondrial dysfunction in type 2 diabetic Goto-Kakizaki (GK) rats: ameliorating effects of (-)-epigallocatechin-3-gallate. The Journal of nutritional biochemistry 92 21820301
2010 Evidence of interaction of CARD8 rs2043211 with NALP3 rs35829419 in Crohn's disease. Genes and immunity 91 20182451
2018 Epigenome-wide DNA methylation regulates cardinal pathological features of psoriasis. Clinical epigenetics 88 30092825
2020 DPP8/9 inhibitors activate the CARD8 inflammasome in resting lymphocytes. Cell death & disease 86 32796818
2018 Loss-of-function CARD8 mutation causes NLRP3 inflammasome activation and Crohn's disease. The Journal of clinical investigation 83 29408806
2006 TUCAN (CARD8) genetic variants and inflammatory bowel disease. Gastroenterology 83 17030188
2017 Mutant Profilin1 transgenic mice recapitulate cardinal features of motor neuron disease. Human molecular genetics 80 28040732
2014 Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012-2013. Malaria journal 76 25471113
2021 Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8. Nature communications 70 33420028
2016 Cardinal Orientation Selectivity Is Represented by Two Distinct Ganglion Cell Types in Mouse Retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 68 26985031
2021 Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes. Nature communications 65 33420033
2011 Interaction of the inflammasome genes CARD8 and NLRP3 in abdominal aortic aneurysms. Atherosclerosis 64 21621776
2008 Different roles for TGF-beta and VEGF in the pathogenesis of the cardinal features of diabetic nephropathy. Diabetes research and clinical practice 64 18842317
2002 TUCAN/CARDINAL and DRAL participate in a common pathway for modulation of NF-kappaB activation. FEBS letters 57 12067710
2019 DPP9's Enzymatic Activity and Not Its Binding to CARD8 Inhibits Inflammasome Activation. ACS chemical biology 53 31525884
2012 Relationship between physicochemical characterization and toxicity of fine particulate matter (PM2.5) collected in Dakar city (Senegal). Environmental research 51 22284916
2014 Environmental surveillance of poliovirus and non-polio enterovirus in urban sewage in Dakar, Senegal (2007-2013). The Pan African medical journal 45 25848458
2006 Molecular epidemiology of hepatitis B virus in Dakar, Sénégal. Journal of medical virology 44 16419106
2008 Novel isoforms of the CARD8 (TUCAN) gene evade a nonsense mutation. European journal of human genetics : EJHG 43 18212821
2020 Activation of the CARD8 Inflammasome Requires a Disordered Region. Cell reports 42 33053349
2014 Liver X receptor: a cardinal target for atherosclerosis and beyond. Journal of atherosclerosis and thrombosis 42 24695022
2024 The CARD8 inflammasome dictates HIV/SIV pathogenesis and disease progression. Cell 41 38428396
2017 Periodic Fever with Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome Is Associated with a CARD8 Variant Unable To Bind the NLRP3 Inflammasome. Journal of immunology (Baltimore, Md. : 1950) 40 28137891
2017 Inflammasomes, the cardinal pathology mediators are activated by pathogens, allergens and mutagens: A critical review with focus on NLRP3. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 40 28599247
2013 Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing spondylitis. Scandinavian journal of rheumatology 40 23547871
2008 Malaria transmission in Dakar: a two-year survey. Malaria journal 40 18796138
2004 Changes in gonadal steroid receptors in the cardinal ligaments of prolapsed uteri: immunohistomorphometric data. Human reproduction (Oxford, England) 40 15142996
2011 Association of CARD8 with inflammatory bowel disease in Koreans. Journal of human genetics 39 21248762
2017 Contralateral Bias of High Spatial Frequency Tuning and Cardinal Direction Selectivity in Mouse Visual Cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 38 28924011
2009 Investigation of innate immunity genes CARD4, CARD8 and CARD15 as germline susceptibility factors for colorectal cancer. BMC gastroenterology 38 19843337
2000 Etiology of genital ulcer disease in Dakar, Senegal, and comparison of PCR and serologic assays for detection of Haemophilus ducreyi. Journal of clinical microbiology 37 10618099
2023 Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome. PLoS biology 36 37289745
2020 The cardinal roles of ferroportin and its partners in controlling cellular iron in and out. Life sciences 36 32712297
2018 Zebrafish mutants and TEAD reporters reveal essential functions for Yap and Taz in posterior cardinal vein development. Scientific reports 36 29976931
2015 Positional cloning of a Bombyx pink-eyed white egg locus reveals the major role of cardinal in ommochrome synthesis. Heredity 36 26328757
2013 Susceptibility to Mycobacterium tuberculosis infection in HIV-positive patients is associated with CARD8 genetic variant. Journal of acquired immune deficiency syndromes (1999) 36 23507658
2010 Caspase recruitment domain-containing protein 8 (CARD8) negatively regulates NOD2-mediated signaling. The Journal of biological chemistry 36 20385562
2022 Viral proteases activate the CARD8 inflammasome in the human cardiovascular system. The Journal of experimental medicine 35 36129453
2013 Association of NLRP3 and CARD8 genetic polymorphisms with juvenile idiopathic arthritis in a Taiwanese population. Scandinavian journal of rheumatology 34 24295199
1988 Exocrine pancreatic function and protein-calorie malnutrition in Dakar and Abidjan (West Africa): silent pancreatic insufficiency. The American journal of clinical nutrition 32 3189210
2019 Prevalence of antimicrobial resistance and potential pathogenicity, and possible spread of third generation cephalosporin resistance, in Escherichia coli isolated from healthy chicken farms in the region of Dakar, Senegal. PloS one 31 30913237
2021 VPS35 D620N knockin mice recapitulate cardinal features of Parkinson's disease. Aging cell 30 33745227
2023 Protein folding stress potentiates NLRP1 and CARD8 inflammasome activation. Cell reports 29 36649711
2017 A cross-sectional quantitative analysis of the natural history of Farber disease: an ultra-orphan condition with rheumatologic and neurological cardinal disease features. Genetics in medicine : official journal of the American College of Medical Genetics 29 29048419
2012 Role of NLRP3 and CARD8 in the regulation of TNF-α induced IL-1β release in vascular smooth muscle cells. International journal of molecular medicine 29 22711073
2012 CARD8 rs2043211 (p.C10X) polymorphism is not associated with disease susceptibility or cardiovascular events in Spanish rheumatoid arthritis patients. DNA and cell biology 29 23088220
2005 A novel isoform of TUCAN is overexpressed in human cancer tissues and suppresses both caspase-8- and caspase-9-mediated apoptosis. Cancer research 29 16204039
2022 M24B aminopeptidase inhibitors selectively activate the CARD8 inflammasome. Nature chemical biology 28 35165443
2001 Prevalence and risk factors of cervicovaginal HIV shedding among HIV-1 and HIV-2 infected women in Dakar, Senegal. Sexually transmitted infections 28 11402227
2000 [Sickle cell disease in children in Dakar, Senegal]. Archives de pediatrie : organe officiel de la Societe francaise de pediatrie 28 10668081
2020 Mutations in cardinal are responsible for the red-1 and peach eye color mutants of the red flour beetle Tribolium castaneum. Biochemical and biophysical research communications 26 32703438
2023 Cardinal features of immune memory in innate lymphocytes. Nature immunology 25 37828377
2020 Ommochrome pathway genes kynurenine 3-hydroxylase and cardinal participate in eye pigmentation in Plutella xylostella. BMC molecular and cell biology 24 32917146
2008 Deficiency of CARD8 is associated with increased Alzheimer's disease risk in women. Dementia and geriatric cognitive disorders 24 18841008
2023 A human-specific motif facilitates CARD8 inflammasome activation after HIV-1 infection. eLife 21 37417868
2022 CRISPR-mediated knockout of cardinal and cinnabar eye pigmentation genes in the western tarnished plant bug. Scientific reports 21 35322099
2015 Expression Quantitative Trait Loci for CARD8 Contributes to Risk of Two Infection-Related Cancers--Hepatocellular Carcinoma and Cervical Cancer. PloS one 21 26147888
2008 No association of the CARD8 (TUCAN) c.30T>A (p.C10X) variant with Crohn's disease: a study in 3 independent European cohorts. Inflammatory bowel diseases 20 18092344
2023 Tripping the wire: sensing of viral protease activity by CARD8 and NLRP1 inflammasomes. Current opinion in immunology 19 37311351
2013 Physico-chemical characterization of African urban aerosols (Bamako in Mali and Dakar in Senegal) and their toxic effects in human bronchial epithelial cells: description of a worrying situation. Particle and fibre toxicology 19 23548138
2015 Is the CARD8 rs2043211 polymorphism associated with susceptibility to Crohn's disease? A meta-analysis. Autoimmunity 18 26462578
2022 A ubiquitin-independent proteasome pathway controls activation of the CARD8 inflammasome. The Journal of biological chemistry 17 35580636
2019 Individual exposure level following indoor and outdoor air pollution exposure in Dakar (Senegal). Environmental pollution (Barking, Essex : 1987) 17 30825765
2018 Oxidative status of cardinal ligament in pelvic organ prolapse. Experimental and therapeutic medicine 17 30250520
2016 Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study. Journal of Korean medical science 17 27550484
2020 Developmental nicotine exposure engenders intergenerational downregulation and aberrant posttranslational modification of cardinal epigenetic factors in the frontal cortices, striata, and hippocampi of adolescent mice. Epigenetics & chromatin 16 32138755
2016 Prevalence of anti-malarial resistance genes in Dakar, Senegal from 2013 to 2014. Malaria journal 16 27387549
2015 Association between CARD8 rs2043211 polymorphism and inflammatory bowel disease: a meta-analysis. Immunological investigations 16 25564880
1998 Decrease in p53 protein in cultured cardinal ligament fibroblasts from patients with prolapsus uteri. Cell biology international 16 9828080
2022 Real-world effectiveness of nivolumab plus ipilimumab and second-line therapy in Japanese untreated patients with metastatic renal cell carcinoma: 2-year analysis from a multicenter retrospective clinical study (J-cardinal study). Japanese journal of clinical oncology 15 35920793
2021 Nurr1 repression mediates cardinal features of Parkinson's disease in α-synuclein transgenic mice. Human molecular genetics 15 33902111
2006 Evaluation of HIV-1 p24 antigenemia and level of CD8+CD38+ T cells as surrogate markers of HIV-1 RNA viral load in HIV-1-infected patients in Dakar, Senegal. Journal of acquired immune deficiency syndromes (1999) 15 16652048
2013 The CARD8 p.C10X mutation associates with a low anti-glycans antibody response in patients with Crohn's disease. BMC medical genetics 14 23506543
1975 Modest radiosensitization of solid tumours in C3H mice by the hypoxic cell radiosensitizer NDPP. British journal of cancer 14 1156512
2021 Cardinal parameter growth and growth boundary model for non-proteolytic Clostridium botulinum - Effect of eight environmental factors. International journal of food microbiology 13 33827003
2020 De Novo Assembly of the Northern Cardinal (Cardinalis cardinalis) Genome Reveals Candidate Regulatory Regions for Sexually Dichromatic Red Plumage Coloration. G3 (Bethesda, Md.) 13 32792344
2020 3-Hydroxykynurenine in Regulation of Drosophila Behavior: The Novel Mechanisms for Cardinal Phenotype Manifestations. Frontiers in physiology 13 32848886
2020 Expression of CARD8 in human atherosclerosis and its regulation of inflammatory proteins in human endothelial cells. Scientific reports 13 33154409
2018 The role of ADAMTS-2, collagen type-1, TIMP-3 and papilin levels of uterosacral and cardinal ligaments in the etiopathogenesis of pelvic organ prolapse among women without stress urinary incontinence. European journal of obstetrics, gynecology, and reproductive biology 13 30388611
2017 Deficiency of a brain-specific chemokine-like molecule, SAM3, induces cardinal phenotypes of autism spectrum disorders in mice. Scientific reports 13 29184127
2024 The long noncoding RNA CARDINAL attenuates cardiac hypertrophy by modulating protein translation. The Journal of clinical investigation 12 38743498
2024 CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity. Cells 12 38920661
2021 Transforming Growth Factor Beta 1 and p44/42 Expression in Cardinal Ligament Tissues of Patients with Pelvic Organ Prolapse. Medical science monitor : international medical journal of experimental and clinical research 12 34176919
2006 TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cells. BMC cancer 12 16796750
1992 Tumor-suppressor genes: cardinal factors in inherited predisposition to human cancers. Environmental health perspectives 12 1336726