Affinage

CARD8

Caspase recruitment domain-containing protein 8 · UniProt Q9Y2G2

Length
537 aa
Mass
60.7 kDa
Annotated
2026-06-09
100 papers in source corpus 25 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CARD8 is a cytosolic inflammasome-forming sensor that couples diverse cytoplasmic threats to caspase-1-dependent pyroptosis through a unique, ASC-independent mechanism (PMID:33420028, PMID:33420033, PMID:33053349). The receptor is held inactive by constitutive autoproteolysis at a conserved SF/S motif within its ZU5-UPA (FIIND) domain, which generates non-covalently associated N-terminal and C-terminal fragments (PMID:22087307). Activation is governed by degradation of the autoinhibitory N-terminal fragment: the ubiquitin-independent 20S proteasome partially degrades the disordered N-terminus in resting cells, and activating stimuli drive its complete destruction, freeing the C-terminal (UPA+CARD) fragment (PMID:33053349, PMID:35580636). The dipeptidyl peptidase DPP9 imposes a second layer of restraint by directly binding CARD8 and enzymatically sequestering the liberated C-terminal fragment, such that both fragment degradation and disruption of the DPP9 complex are required for the C-terminus to self-oligomerize into helical CARD filaments that directly recruit and activate pro-caspase-1, triggering gasdermin D-mediated death (PMID:31525884, PMID:36649711, PMID:33420028, PMID:33420033). This sensor detects DPP8/9 inhibition—including proline-peptide accumulation downstream of the M24B aminopeptidases PEPD and XPNPEP1—and protein-folding stress, and acts as a tripwire for viral proteases: HIV-1 protease, SARS-CoV-2 and coronavirus 3CL proteases, and Coxsackievirus B3/picornavirus 2A and 3C proteases cleave the rapidly evolving CARD8 N-terminus to trigger pyroptosis of infected or virion-exposed cells (PMID:35165443, PMID:33542150, PMID:37289745, PMID:36129453, PMID:38428396). This drives pyroptosis of resting CD4+ and CD8+ T cells and contributes to T-cell depletion and clearance of latent HIV-1, while T-cell activation abolishes CARD8 function (PMID:32840892, PMID:33542150, PMID:38428396). Beyond inflammasome sensing, CARD8 functions as an anti-inflammatory scaffold: it binds and inhibits NLRP3, preventing its deubiquitination, dephosphorylation, and oligomerization, with disease-associated mutations (V44I, frameshift truncations) disrupting NLRP3 binding via the FIIND/CARD region (PMID:24517500, PMID:29408806, PMID:28137891). Earlier studies also reported CARD8 binding to caspase-1, NOD2 (blocking nodosome assembly and bactericidal activity), and components of the NF-κB pathway (PMID:11821383, PMID:20385562, PMID:12067710).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2002 Medium

    Established the founding hypothesis that CARD8 is a negative regulator of inflammatory and apoptotic caspases, framing it initially as an inhibitory CARD scaffold.

    Evidence Co-IP and IL-1β/caspase activity assays in monocytic and transfected cells linking CARD8 to caspase-1, caspase-9, and NF-κB pathways

    PMID:11408476 PMID:11821383 PMID:12067710

    Open questions at the time
    • Largely overexpression-based; physiological relevance of caspase-9/NF-κB inhibition not established in primary cells
    • Caspase-9 binding later contradicted in NSCLC cells
  2. 2005 Medium

    Showed isoform-specific function, with a 54 kDa TUCAN isoform binding FADD and inhibiting both caspase-8 and caspase-9, indicating that the CARD8 protein repertoire diversifies its regulatory targets.

    Evidence Co-IP, siRNA, and caspase/cell-death assays comparing 54 kDa vs 48 kDa isoforms

    PMID:16204039

    Open questions at the time
    • Single-lab overexpression data
    • Endogenous relevance of the 54 kDa isoform not defined
  3. 2006 Medium

    Challenged the early caspase-9 inhibition model by failing to reproduce CARD8–procaspase-9 binding or functional effects in a different cellular context.

    Evidence Negative Co-IP and siRNA caspase-9 activity/viability assays in NSCLC cells

    PMID:16796750

    Open questions at the time
    • Negative result in one cell type; does not exclude context-dependent interaction
    • Does not resolve which cellular settings, if any, support caspase-9 regulation
  4. 2008 Medium

    Resolved an apparent loss-of-function SNP paradox by showing alternative N-terminal exons circumvent the C10X stop codon, so CARD8 protein is still expressed in stop-allele homozygotes.

    Evidence RT-PCR, EST mining, immunoblot, and SNP genotyping defining ~47–60 kDa isoforms

    PMID:18212821

    Open questions at the time
    • Functional consequences of each isoform not dissected
    • Does not establish tissue-specific isoform usage
  5. 2010 High

    Extended CARD8's inhibitory scaffold role to innate bacterial sensing by showing it restrains NOD2-driven nodosome assembly and bactericidal activity.

    Evidence Reciprocal Co-IP, siRNA, NF-κB reporter, and intracellular Listeria killing assays in intestinal epithelial cells

    PMID:20385562

    Open questions at the time
    • Structural basis of CARD8–NOD2 interaction undefined
    • In vivo relevance not tested
  6. 2011 High

    Defined the biochemical basis of CARD8 regulation by identifying constitutive autoproteolysis at the FIIND SF/S motif, establishing the two-fragment architecture that underlies later activation models.

    Evidence Site-directed mutagenesis of the catalytic serine and flanking residues with immunoblot detection of cleavage; structural modeling identifying the ZU5-UPA domain

    PMID:22087307

    Open questions at the time
    • Functional consequence of fragment generation not yet linked to inflammasome activation
    • No atomic structure of the FIIND at this stage
  7. 2014 High

    Anchored CARD8 as an endogenous NLRP3 brake by demonstrating selective binding to wild-type NLRP3 and suppression of IL-1β, with endogenous association in primary cells.

    Evidence Reciprocal Co-IP in HEK293 and PBMCs, IL-1β ELISA, siRNA in human macrophages

    PMID:24517500

    Open questions at the time
    • Mechanism by which CAPS mutations escape CARD8 binding unresolved at this point
    • Which CARD8 domain mediates NLRP3 binding not yet mapped
  8. 2017 Medium

    Mapped the structural requirement for NLRP3 inhibition by showing a frameshift variant lacking FIIND/CARD cannot bind NLRP3's NOD domain.

    Evidence NGS, binding assays, and domain truncation analysis

    PMID:28137891

    Open questions at the time
    • Single-lab binding data
    • Disease causality of the variant not established by rescue
  9. 2018 High

    Provided molecular and patient-level mechanism for CARD8-driven autoinflammation, showing the V44I mutation abolishes NLRP3 binding and acts dominant-negatively, and that intact CARD8 blocks NLRP3 deubiquitination and dephosphorylation.

    Evidence Whole-exome sequencing, immunoprecipitation, NLRP3 oligomerization/PTM immunoblots, patient monocyte IL-1β assays

    PMID:29408806

    Open questions at the time
    • How CARD8 controls NLRP3 PTM enzymatically undefined
    • Genetic causality across larger cohorts not addressed
  10. 2019 High

    Distinguished CARD8 from NLRP1 by showing DPP9 restrains it through enzymatic activity rather than simple binding, since DPP8/9 inhibitors and autoproteolysis mutants do not disrupt the DPP9–CARD8 interaction.

    Evidence Activity-based probes, reconstituted cell-death assays, MS proteomics, catalytically inactive DPP9 rescue in knockout cells

    PMID:31525884

    Open questions at the time
    • Structural basis of DPP9–CARD8 distinct from DPP9–NLRP1 not resolved here
    • Identity of the relevant DPP9 substrate/product unclear
  11. 2020 High

    Identified the activation switch as proteasomal destruction of the autoinhibitory N-terminal fragment that frees the C-terminus, and demonstrated CARD8-driven pyroptosis in primary resting T cells upon DPP8/9 inhibition.

    Evidence Domain deletion mapping, proteasome inhibition, and immunoblot of fragment degradation; CRISPR/siRNA of CARD8/caspase-1/GSDMD in primary CD4+/CD8+ T cells across species

    PMID:32796818 PMID:32840892 PMID:33053349

    Open questions at the time
    • Why activated T cells become resistant not fully explained
    • Identity of the degradation machinery recognizing the NT fragment not yet defined
  12. 2021 High

    Resolved the activation mechanism structurally and established CARD8 as a viral-protease sensor: the C-terminal UPA+CARD self-assembles into helical filaments that recruit caspase-1 directly without ASC, and HIV-1 protease cleavage triggers pyroptosis enabling latent reservoir clearance.

    Evidence Cryo-EM of CARD8-CARD filaments with biochemical/cell-based caspase-1 recruitment assays; CRISPR knockout and pharmacological HIV protease activation in patient CD4+ T cells

    PMID:33420028 PMID:33420033 PMID:33542150

    Open questions at the time
    • Stoichiometry of filament-to-caspase-1 activation in cells not quantified
    • Therapeutic window of latency-clearance approach not defined
  13. 2022 High

    Mechanistically connected upstream metabolism and broader pathogen sensing to CARD8, defining the 20S proteasome as the degrading enzyme, the PEPD/XPNPEP1–proline-peptide–DPP8/9 axis as a selective trigger, and CVB3 2A/3C proteases as activators in cardiovascular cells.

    Evidence Proteasome subunit knockdown/inhibitors with fragment immunoblots; CQ31 chemical biology with MS peptide profiling and genetic knockouts; CRISPR knockout and cleavage-site mapping in endothelial cells and cardiomyocytes

    PMID:35165443 PMID:35580636 PMID:36129453

    Open questions at the time
    • How ZU5 unfolding licenses complete NT degradation not structurally resolved
    • In vivo contribution of CARD8 to viral myocarditis not established
  14. 2023 High

    Generalized CARD8 to a broadly tuned, rapidly evolving viral-protease tripwire and dissected the two-step activation requirement (NT degradation plus DPP9-complex disruption) under folding stress.

    Evidence CRISPR knockout, protease cleavage assays, comparative evolutionary/SNP analysis for SARS-CoV-2 and picornavirus 3C/3CL proteases and HIV-1; immunoblot of NT/CT fragments with DPP9 binding and cell-death assays under stress agents

    PMID:36649711 PMID:37289745 PMID:37417868

    Open questions at the time
    • Endogenous physiological inducers of protein-folding-stress activation in vivo unclear
    • Functional consequences of human SNPs at population scale not defined
  15. 2024 High

    Demonstrated in vivo significance by showing virion-delivered HIV-1 protease activates CARD8 immediately at entry to kill quiescent CD4+ T cells, with CARD8-deficient humanized mice showing delayed CD4+ depletion and natural-host primates carrying CARD8 loss-of-function alleles.

    Evidence CARD8-knockout humanized mice, primary CD4+ T-cell entry assays with protease inhibitors, non-human primate CARD8 sequencing, cell-death assays

    PMID:38428396

    Open questions at the time
    • Net effect of CARD8 activity on HIV pathogenesis (protective vs depleting) not fully reconciled
    • Therapeutic implications of modulating CARD8 in HIV not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CARD8's anti-inflammatory scaffolding functions (NLRP3, NOD2, NF-κB regulation) mechanistically integrate with or are switched to its inflammasome-sensing role remains unresolved.
  • No unified model linking scaffold inhibition and filament-forming activation
  • Enzymatic basis for CARD8 control of NLRP3 deubiquitination/dephosphorylation unknown
  • Structural basis of CARD8–NLRP3 and CARD8–NOD2 interactions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 1 GO:0140096 catalytic activity, acting on a protein 1 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
CASP1CASP9DPP9FADDNLRP3NOD2
Complex memberships
CARD8 inflammasomeCARD8-CARD filament

Evidence

Reading pass · 24 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, two other negative regulators of caspase-1. Co-immunoprecipitation, overexpression in THP-1/U937 cells, ELISA for IL-1β The Journal of Biological Chemistry Medium 11821383
2001 CARD8 (TUCAN) CARD domain selectively binds procaspase-9 and interferes with Apaf-1–procaspase-9 interaction, suppressing caspase activation induced by cytochrome c/Apaf-1-dependent stimuli (Bax, VP16, staurosporine) but not Apaf-1-independent stimuli (Fas, granzyme B). Co-immunoprecipitation, stable/transient transfection, caspase activity assays, apoptosis assays The Journal of Biological Chemistry Medium 11408476
2002 CARD8 (TUCAN/CARDINAL) associates with DRAL and suppresses NF-κB activation; DRAL expression enhances NF-κB activity, suggesting DRAL and CARD8 participate in a common regulatory pathway controlling NF-κB. Co-immunoprecipitation, NF-κB reporter assay, overexpression FEBS Letters Medium 12067710
2005 A novel 54 kDa TUCAN isoform (TUCAN-54) suppresses both caspase-8 and caspase-9 activation; TUCAN-54 physically associates with Fas-associated death domain (FADD) — an interaction not seen with 48 kDa TUCAN — thereby inhibiting Fas-induced cell death in addition to mitochondrial pathway apoptosis. Co-immunoprecipitation, gene transfection/siRNA, caspase activity assays, cell death assays Cancer Research Medium 16204039
2010 CARD8 physically interacts with NOD2 and inhibits nodosome assembly and downstream NF-κB signaling upon muramyl-dipeptide (MDP) stimulation; CARD8 also inhibits the direct bactericidal effect of NOD2 against intracellular Listeria monocytogenes infection. Co-immunoprecipitation, siRNA knockdown, NF-κB reporter assay, intracellular bacterial killing assay in intestinal epithelial cells The Journal of Biological Chemistry High 20385562
2011 CARD8 and NLRP1 undergo autoproteolytic cleavage at a conserved SF/S motif within their FIIND domain; site-directed mutagenesis showed the second serine of this motif is required for autoproteolysis, and conserved glutamic acid and histidine residues near the cleavage site regulate processing efficiency. Structural modeling identified FIIND as a ZU5-UPA domain. Site-directed mutagenesis, immunoblot detection of cleavage products, bioinformatics/structural modeling PLoS One High 22087307
2014 CARD8 interacts with wild-type NLRP3 but not with CAPS-associated mutant forms of NLRP3; CARD8 significantly reduces IL-1β secretion driven by wild-type NLRP3 but not mutant NLRP3; endogenous CARD8–NLRP3 association was confirmed in resting PBMCs; CARD8 knockdown increased IL-1β secretion from human macrophages. Co-immunoprecipitation (HEK293 and primary PBMCs), ELISA for IL-1β, siRNA knockdown in human monocyte-derived macrophages Arthritis Research & Therapy High 24517500
2017 A CARD8 frameshift variant (CARD8-FS) produces a truncated protein lacking the FIIND and CARD domains; this truncated protein fails to interact with the NOD domain of NLRP3, demonstrating that the FIIND/CARD region of CARD8 is required for NLRP3 binding and inflammasome inhibition. Next-generation sequencing, immunoprecipitation/binding assay, domain truncation analysis Journal of Immunology Medium 28137891
2018 A V44I missense mutation in the T60 isoform of CARD8 prevents its binding to NLRP3 and inhibition of NLRP3 oligomerization; mutant T60 CARD8 also exerts a dominant-negative effect by forming oligomers with wild-type T60 and T48 CARD8 that prevent their NLRP3 binding. Intact CARD8 prevents NLRP3 deubiquitination and serine dephosphorylation. Whole exome sequencing, immunoprecipitation, immunoblot for NLRP3 oligomerization and post-translational modifications, patient monocyte functional assays (IL-1β ELISA) The Journal of Clinical Investigation High 29408806
2019 DPP9 binds directly to CARD8 but, unlike DPP9–NLRP1, the DPP9–CARD8 interaction is not disrupted by DPP8/9 inhibitors or by CARD8 mutations that block autoproteolysis; catalytically inactive DPP9 fails to rescue CARD8-mediated cell death in DPP9 knockout cells, demonstrating that DPP9's enzymatic activity (not merely its binding to CARD8) restrains the CARD8 inflammasome. Activity-based probes, reconstituted inflammasome cell-death assays, mass spectrometry proteomics, DPP9 knockout cells ACS Chemical Biology High 31525884
2020 DPP8/9 inhibitor Val-boroPro triggers CARD8 inflammasome-dependent pyroptosis in primary human resting CD4+ and CD8+ T cells via the CARD8–caspase-1–GSDMD axis; DPP9 is the relevant DPP restraining CARD8 activation in T cells. Activated T cells are resistant despite expressing all required components. Genetic dissection in primary T cells (CRISPR/siRNA knockdown of CARD8, caspase-1, GSDMD), cell death morphology/biochemistry, immunoblot The EMBO Journal High 32840892
2020 DPP8/9 inhibitors activate CARD8-mediated pyroptosis in resting human and rodent lymphocytes (CD4+ and CD8+ T cells); species-specific variation in T cell sensitivity is observed. Pharmacological inhibition, genetic validation (CARD8 knockdown), cell viability assays across species Cell Death & Disease Medium 32796818
2020 DPP8/9 inhibition activates a proteasomal degradation pathway targeting CARD8's N-terminal disordered region (~160 amino acids); degradation of the N-terminal fragment frees the C-terminal fragment to activate caspase-1 and induce pyroptosis. CARD8 thus serves as a sensor of activation of a degradation pathway for disordered/misfolded proteins. Domain mapping/deletion analysis, proteasome inhibition, cell death assays, immunoblot for fragment degradation Cell Reports High 33053349
2021 CARD8 senses HIV-1 protease activity; premature intracellular activation of the viral protease triggers CARD8 inflammasome-mediated pyroptosis of HIV-1-infected cells, enabling clearance of latent HIV-1 in patient CD4+ T cells after viral reactivation. CRISPR knockout of CARD8, pharmacological HIV protease activation, cell death assays, patient CD4+ T cell latency clearance model Science High 33542150
2021 Cryo-EM structures of CARD8-CARD filaments (3.7 Å) reveal that CARD8-CT (UPA+CARD) self-oligomerizes to form helical filaments; CARD8 directly recruits pro-caspase-1 (not ASC) via unique CARD–CARD interactions, distinguishing CARD8 from NLRP1 which requires ASC. The UPA subdomain lowers the threshold for CARD filament formation. Cryo-EM structure determination, biochemical reconstitution, cell-based ASC speck/caspase-1 recruitment assays Nature Communications High 33420028 33420033
2022 The core 20S proteasome (ubiquitin-independent) degrades the disordered N-terminal region of CARD8; in unstimulated cells, partial degradation of the disordered region leaves a folded ZU5/UPA/CARD inhibitory fragment, but Val-boroPro stress causes complete NT degradation (possibly via ZU5 unfolding), releasing the CT fragment to activate the inflammasome. Proteasome subunit knockdown, 20S proteasome inhibitors, immunoblot of CARD8 fragments, cell death assays, domain mutants The Journal of Biological Chemistry High 35580636
2022 M24B aminopeptidases prolidase (PEPD) and XPNPEP1 are upstream regulators of CARD8; their inhibition by CQ31 leads to accumulation of proline-containing peptides that inhibit DPP8/9, selectively activating CARD8 but not NLRP1 (because NLRP1 directly contacts DPP8/9's active site and proline peptides cannot disrupt this). Chemical biology (selective inhibitor CQ31), DPP8/9 activity assays, mass spectrometry for peptide accumulation, CARD8/NLRP1 cell death assays, genetic knockouts Nature Chemical Biology High 35165443
2022 CARD8 inflammasome is activated in human endothelial cells and cardiomyocytes by Coxsackievirus B3 (CVB3) 2A and 3C proteases cleaving CARD8 at p.G38; CARD8 genetic deletion in endothelial cells and cardiomyocytes attenuates CVB3-induced pyroptosis, inflammation, and viral propagation. CRISPR knockout of CARD8 in endothelial cells and hESC-derived cardiomyocytes, protease cleavage site mapping, cell death assays, viral propagation assay, co-culture system The Journal of Experimental Medicine High 36129453
2023 SARS-CoV-2 and diverse coronaviruses 3CL protease cleaves a rapidly evolving region of human CARD8, activating a robust inflammasome response; CARD8 is required for cell death and pro-inflammatory cytokine release during SARS-CoV-2 infection. Natural variation in this 'tripwire' region alters species-specific sensing (e.g., 3CLpro antagonizes rather than activates megabat CARD8), and a human SNP reduces CARD8 sensing of coronavirus 3CLpros while enabling sensing of select picornavirus 3C proteases. CRISPR knockout, protease cleavage assays, inflammasome activation assays, comparative evolutionary analysis, SNP functional characterization PLoS Biology High 37289745
2023 HIV-1 protease cleaves the CARD8 N-terminus at a site unique to humans (arising after the human–chimpanzee divergence); cleavage by both de novo translated HIV-1 protease and packaged virion-associated protease activates CARD8 pyroptosis. TLR stimulation prior to infection modulates the magnitude of CARD8-induced pyroptosis. SIVcpz cleaves human CARD8 despite not activating chimpanzee CARD8, suggesting SIVcpz was poised to activate human CARD8 before cross-species transmission. Protease cleavage site mapping, CARD8 knockout/knockin, evolutionary sequence analysis, cell death assays with packaged vs. de novo HIV protease eLife High 37417868
2023 Several agents that cause protein folding stress (aminopeptidase inhibitors, chaperone inhibitors, unfolded protein response inducers) accelerate CARD8 N-terminal fragment degradation; however, the released C-terminal fragments are sequestered by DPP9, and DPP9-binding ligands must additionally be present to disrupt DPP9–CARD8 CT complexes and allow CT oligomerization into active inflammasomes. Immunoblot of NT/CT fragment levels, pharmacological stress agents, DPP9 binding assays, cell death assays Cell Reports Medium 36649711
2024 The CARD8 inflammasome is activated immediately after HIV entry by viral protease activity from incoming virions (before de novo viral replication); CARD8 sensing leads to pyroptosis of quiescent CD4+ T cells without productive infection, while T cell activation abolishes CARD8 function and increases permissiveness to infection. In humanized mice reconstituted with CARD8-deficient cells, CD4+ T cell depletion is delayed despite high viremia. 'Natural host' sooty mangabeys harbor loss-of-function CARD8 mutations, potentially explaining non-pathogenic SIV infection. CARD8 knockout humanized mice, primary CD4+ T cell assays, HIV entry experiments with protease inhibitors, CARD8 sequencing in non-human primates, cell death assays Cell High 38428396
2006 TUCAN (CARD8) interactions with procaspase-9 could not be demonstrated by co-immunoprecipitation or other protein interaction assays in NSCLC cells; siRNA-mediated knockdown of TUCAN did not restore cisplatin-induced caspase-9 activation or affect cisplatin sensitivity, indicating TUCAN does not inhibit procaspase-9 in this cellular context (NEGATIVE RESULT). Co-immunoprecipitation, siRNA knockdown, caspase-9 activity assay, cell viability assay BMC Cancer Medium 16796750
2008 The CARD8 rs2043211 (C10X) stop-codon SNP does not abolish all CARD8 protein expression; novel CARD8 mRNA isoforms (conserved in primates) contain alternative N-terminal coding exons that circumvent the stop codon, yielding protein isoforms of ~47–60 kDa. Homozygous stop-allele subjects still express a 48 kDa CARD8 isoform. RT-PCR, EST database mining, immunoblot, SNP genotyping European Journal of Human Genetics Medium 18212821

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 CARD8 and NLRP1 undergo autoproteolytic processing through a ZU5-like domain. PloS one 175 22087307
2020 The NLRP1 and CARD8 inflammasomes. Immunological reviews 150 32558991
2002 CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis. The Journal of biological chemistry 150 11821383
1996 Extensive genetic diversity of Plasmodium falciparum isolates collected from patients with severe malaria in Dakar, Senegal. Transactions of the Royal Society of Tropical Medicine and Hygiene 139 9015525
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.) 135 33542150
2020 CARD8 inflammasome activation triggers pyroptosis in human T cells. The EMBO journal 132 32840892
2013 Pfhrp2 and pfhrp3 polymorphisms in Plasmodium falciparum isolates from Dakar, Senegal: impact on rapid malaria diagnostic tests. Malaria journal 115 23347727
2001 TUCAN, an antiapoptotic caspase-associated recruitment domain family protein overexpressed in cancer. The Journal of biological chemistry 98 11408476
2014 Regulation of CARD8 expression by ANRIL and association of CARD8 single nucleotide polymorphism rs2043211 (p.C10X) with ischemic stroke. Stroke 94 24385277
2014 CARD8 is a negative regulator for NLRP3 inflammasome, but mutant NLRP3 in cryopyrin-associated periodic syndromes escapes the restriction. Arthritis research & therapy 91 24517500
2010 Evidence of interaction of CARD8 rs2043211 with NALP3 rs35829419 in Crohn's disease. Genes and immunity 91 20182451
2020 DPP8/9 inhibitors activate the CARD8 inflammasome in resting lymphocytes. Cell death & disease 90 32796818
2018 Loss-of-function CARD8 mutation causes NLRP3 inflammasome activation and Crohn's disease. The Journal of clinical investigation 85 29408806
2006 TUCAN (CARD8) genetic variants and inflammatory bowel disease. Gastroenterology 83 17030188
2006 Urban malaria in Dakar, Senegal: chemosusceptibility and genetic diversity of Plasmodium falciparum isolates. The American journal of tropical medicine and hygiene 77 16837722
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 74 33420028
2021 Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes. Nature communications 68 33420033
2011 Interaction of the inflammasome genes CARD8 and NLRP3 in abdominal aortic aneurysms. Atherosclerosis 64 21621776
1999 Risk factors for negative sputum acid-fast bacilli smears in pulmonary tuberculosis: results from Dakar, Senegal, a city with low HIV seroprevalence. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease 58 10206504
2002 TUCAN/CARDINAL and DRAL participate in a common pathway for modulation of NF-kappaB activation. FEBS letters 57 12067710
2000 Tuberculosis-associated severe CD4+ T-lymphocytopenia in HIV-seronegative patients from Dakar. SIDAK Research Group. The Journal of infection 56 11023763
2019 DPP9's Enzymatic Activity and Not Its Binding to CARD8 Inhibits Inflammasome Activation. ACS chemical biology 54 31525884
2015 Emergence of Mutations in the K13 Propeller Gene of Plasmodium falciparum Isolates from Dakar, Senegal, in 2013-2014. Antimicrobial agents and chemotherapy 52 26503652
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 47 25848458
2006 Molecular epidemiology of hepatitis B virus in Dakar, Sénégal. Journal of medical virology 45 16419106
2020 Activation of the CARD8 Inflammasome Requires a Disordered Region. Cell reports 44 33053349
2008 Novel isoforms of the CARD8 (TUCAN) gene evade a nonsense mutation. European journal of human genetics : EJHG 43 18212821
2024 The CARD8 inflammasome dictates HIV/SIV pathogenesis and disease progression. Cell 42 38428396
2012 Epidemiology of Staphylococcus aureus in pigs and farmers in the largest farm in Dakar, Senegal. Foodborne pathogens and disease 42 22953738
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) 41 28137891
2013 Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing spondylitis. Scandinavian journal of rheumatology 41 23547871
2012 Prevalence of molecular markers of Plasmodium falciparum drug resistance in Dakar, Senegal. Malaria journal 40 22694921
2008 Malaria transmission in Dakar: a two-year survey. Malaria journal 40 18796138
2011 Association of CARD8 with inflammatory bowel disease in Koreans. Journal of human genetics 39 21248762
2009 Investigation of innate immunity genes CARD4, CARD8 and CARD15 as germline susceptibility factors for colorectal cancer. BMC gastroenterology 38 19843337
2023 Host-specific sensing of coronaviruses and picornaviruses by the CARD8 inflammasome. PLoS biology 37 37289745
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
2022 Viral proteases activate the CARD8 inflammasome in the human cardiovascular system. The Journal of experimental medicine 36 36129453
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
2013 Association of NLRP3 and CARD8 genetic polymorphisms with juvenile idiopathic arthritis in a Taiwanese population. Scandinavian journal of rheumatology 34 24295199
2006 Seroprevalence and molecular epidemiology of human T-Cell leukemia virus type 1 (HTLV-1) and HTLV-2 in blood donors from Dakar, Senegal. Journal of clinical microbiology 32 16597891
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
2011 Conditions of malaria transmission in Dakar from 2007 to 2010. Malaria journal 31 22018223
2001 Primary prevention with cotrimoxazole for HIV-1-infected adults: results of the pilot study in Dakar, Senegal. Journal of acquired immune deficiency syndromes (1999) 31 11242179
2023 Protein folding stress potentiates NLRP1 and CARD8 inflammasome activation. Cell reports 30 36649711
2022 M24B aminopeptidase inhibitors selectively activate the CARD8 inflammasome. Nature chemical biology 29 35165443
2013 CARD8 gene encoding a protein of innate immunity is expressed in human atherosclerosis and associated with markers of inflammation. Clinical science (London, England : 1979) 29 23611467
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
2001 Prevalence and risk factors of cervicovaginal HIV shedding among HIV-1 and HIV-2 infected women in Dakar, Senegal. Sexually transmitted infections 29 11402227
2000 [Sickle cell disease in children in Dakar, Senegal]. Archives de pediatrie : organe officiel de la Societe francaise de pediatrie 28 10668081
1995 Loss of muscle oxidative capacity after an extreme endurance run: the Paris-Dakar foot-race. International journal of sports medicine 28 7591382
2015 Emerging knock-down resistance in Anopheles arabiensis populations of Dakar, Senegal: first evidence of a high prevalence of kdr-e mutation in West African urban area. Malaria journal 27 26395241
2009 Evaluation of group genetic ancestry of populations from Philadelphia and Dakar in the context of sex-biased admixture in the Americas. PloS one 27 19946364
2016 Nutrient Intake Is Insufficient among Senegalese Urban School Children and Adolescents: Results from Two 24 h Recalls in State Primary Schools in Dakar. Nutrients 26 27775598
2013 Plasmodium falciparum susceptibility to anti-malarial drugs in Dakar, Senegal, in 2010: an ex vivo and drug resistance molecular markers study. Malaria journal 25 23510258
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 23 37417868
2018 Insecticide resistance in Anopheles arabiensis populations from Dakar and its suburbs: role of target site and metabolic resistance mechanisms. Malaria journal 23 29544491
2016 Genotyping and differential expression analysis of inflammasome genes in sporadic malignant melanoma reveal novel contribution of CARD8, IL1B and IL18 in melanoma susceptibility and progression. Cancer genetics 22 27810076
2015 Expression Quantitative Trait Loci for CARD8 Contributes to Risk of Two Infection-Related Cancers--Hepatocellular Carcinoma and Cervical Cancer. PloS one 21 26147888
2013 Anthropometric and micronutrient status of school-children in an urban West Africa setting: a cross-sectional study in Dakar (Senegal). PloS one 21 24391938
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 20 23548138
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
2022 A ubiquitin-independent proteasome pathway controls activation of the CARD8 inflammasome. The Journal of biological chemistry 18 35580636
2015 Is the CARD8 rs2043211 polymorphism associated with susceptibility to Crohn's disease? A meta-analysis. Autoimmunity 18 26462578
2019 Individual exposure level following indoor and outdoor air pollution exposure in Dakar (Senegal). Environmental pollution (Barking, Essex : 1987) 17 30825765
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
2005 [Epidemiological and clinical aspects of paediatric HIV infections in Albert-Royer Paediatric Hospital (Dakar, Senegal)]. Archives de pediatrie : organe officiel de la Societe francaise de pediatrie 17 15808429
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
2017 Genetic Background of the Sickle Cell Disease Pediatric Population of Dakar, Senegal, and Characterization of a Novel Frameshift β-Thalassemia Mutation [HBB: c.265_266del; p.Leu89Glufs*2]. Hemoglobin 15 28670947
2007 Genotypic characterization of antibiotic-resistant Salmonella enteritidis isolates in Dakar, Senegal. Journal of infection in developing countries 15 19734606
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
2003 Evaluation of the seroprevalence of rubella in the region of Dakar (Senegal). Tropical medicine & international health : TM & IH 15 12869096
2001 [Neonatal bacterial infections at the CUH of Dakar]. Gynecologie, obstetrique & fertilite 15 11462959
1999 New results in clinical severity of homozygous sickle cell anemia, in Dakar, Senegal. Hematology and cell therapy 15 10651122
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
2020 Expression of CARD8 in human atherosclerosis and its regulation of inflammatory proteins in human endothelial cells. Scientific reports 13 33154409
2003 [Management of children with sickle cell disease in Africa: experience in a cohort of children at the Royal Albert Hospital in Dakar]. Medecine tropicale : revue du Corps de sante colonial 13 14763308
2024 CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity. Cells 12 38920661
2020 Meeting report: WHO consultation on accelerating Lassa fever vaccine development in endemic countries, Dakar, 10-11 September 2019. Vaccine 12 31952873
2016 Non-falciparum malaria in Dakar: a confirmed case of Plasmodium ovale wallikeri infection. Malaria journal 12 27557982
2006 TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cells. BMC cancer 12 16796750
2003 [Homozygous sickle cell disease in patients above 20 years of age: follow-up of 108 patients in Dakar]. La Revue de medecine interne 12 14604747
2000 [Prevalence of hepatitis B and C viruses in a chronic hemodialysis center in Dakar]. Dakar medical 12 14666779
2022 Sensitivity and specificity for malaria classification of febrile persons by rapid diagnostic test, microscopy, parasite DNA, histidine-rich protein 2, and IgG: Dakar, Senegal 2015. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 11 35504551
2020 Combined polymorphisms in genes encoding the inflammasome components NLRP3 and CARD8 confer risk of ischemic stroke in men. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 11 32689633
2019 Investigation of NF-κB-94ins/del ATTG and CARD8 (rs2043211) Gene Polymorphism in Acute Lymphoblastic Leukemia. Frontiers in endocrinology 11 31428046
2019 A Comparative Study on Phenotypic versus ITS-Based Molecular Identification of Dermatophytes Isolated in Dakar, Senegal. International journal of microbiology 11 31933647
2017 NLRP3 p.Q705K and CARD8 p.C10X single nucleotide polymorphisms are not associated with susceptibility to rheumatoid arthritis: a meta-analysis. International journal of rheumatic diseases 11 28185410
2015 CARD8 gene variant is a risk factor for recurrent surgery in patients with Crohn's disease. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 11 26283210

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