Affinage

Showing CARD10 — CARMA3 is a alias.

CARD10

Caspase recruitment domain-containing protein 10 · UniProt Q9BWT7

Length
1032 aa
Mass
115.9 kDa
Annotated
2026-06-09
61 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CARD10 (CARMA3) is a MAGUK/CARD-domain scaffold protein that nucleates the CARMA3–BCL10–MALT1 (CBM) signalosome to couple cell-surface receptor activation to canonical NF-κB signaling in non-lymphoid cells (PMID:11387339, PMID:11259443). It binds BCL10 through its N-terminal CARD domain, and BCL10 in turn bridges to MALT1 to form a ternary complex that activates the IκB kinases (PMID:11387339). CARMA3 physically associates with IKKγ/NEMO and assembles a large inducible complex containing NEMO and IKKα/β, linking NEMO to TRAF6 to drive polyubiquitination that activates IKK kinase activity (PMID:15184390, PMID:17438001). This CBM module transduces signals from a range of G-protein-coupled receptors—including the angiotensin II type 1 receptor, LPA receptor, PAR-1, CXCR2, and CXCR4—as well as the EGF receptor, typically via PKCα activation (PMID:17101977, PMID:17724468, PMID:21041303, PMID:21406399), and the complex is negatively regulated by A20-mediated deubiquitylation and by MALT1 cleavage of CARD10 at R587, a built-in feedback that dampens NF-κB output (PMID:18349075, PMID:33824280). Through these receptors CARMA3 drives inflammatory and tumor-promoting programs in vascular, epithelial, and cancer cells, including ICAM-1/VCAM-1-dependent monocyte adhesion, VEGF induction, proasthmatic cytokine production, and proliferation/invasion (PMID:21041303, PMID:19112107, PMID:26041536, PMID:21406399), and in vivo CARMA3/BCL10 loss protects against Ang II-driven atherosclerosis and aortic aneurysm (PMID:20605784). CARMA3 additionally exerts NF-κB-independent roles: it sequesters MAVS to balance NF-κB versus IRF3 antiviral responses (PMID:26947079), interacts with IP3 receptors to control calcium-dependent type 2 immune signaling in airway epithelium (PMID:29958012), localizes to mitochondria to preserve mitochondrial integrity in liver sinusoidal endothelial cells (PMID:35831018), and interacts with STAT1 to suppress myofibroblast activation in cardiac fibroblasts (PMID:41053092). CARD10 is itself a direct transcriptional target of the myeloid factor CEBPE and contributes to granulopoiesis (PMID:29773596).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2001 High

    Established CARD10 as a CARD-domain scaffold that physically links BCL10 and MALT1 into a ternary complex and places it upstream of IKK in the PKC-to-NF-κB axis, defining its core molecular role.

    Evidence Co-immunoprecipitation, domain mapping, and dominant-negative mutants with NF-κB reporter assays

    PMID:11259443 PMID:11387339

    Open questions at the time
    • Did not define the receptor that physiologically engages the complex
    • Mechanism connecting the CBM complex to IKK activation not yet resolved
  2. 2004 High

    Showed CARMA3 directly contacts IKKγ/NEMO within a large inducible IKK-containing complex, providing the physical bridge from the scaffold to the kinase machinery.

    Evidence Reciprocal Co-IP and dominant-negative NEMO-binding fragment in NF-κB reporter assays in non-lymphoid cells

    PMID:15184390

    Open questions at the time
    • Did not establish the ubiquitin enzymology activating IKK
    • Upstream receptor input still undefined
  3. 2006 High

    Identified the angiotensin II type 1 GPCR as a physiological trigger for CBM-dependent NF-κB activation, defining CARMA3 as a GPCR effector via NEMO ubiquitination.

    Evidence Dominant-negative mutants, RNAi, Bcl10−/− mice, and in vivo cytokine assays in hepatocytes

    PMID:17101977

    Open questions at the time
    • Did not detail the ubiquitin ligase machinery
    • Generality across other GPCRs not yet tested
  4. 2007 High

    Genetic knockout established CARMA3 as broadly required for GPCR-induced IKK activation and implicated TRAF6 in linking NEMO to its polyubiquitination.

    Evidence CARMA3 knockout mice, Co-IP, ubiquitination and IKK kinase assays

    PMID:17438001

    Open questions at the time
    • Direct demonstration of TRAF6 as the operative ligase incomplete
    • Did not address receptor-specific assembly differences
  5. 2007 High

    Defined PKCα as the specific upstream kinase coupling the LPA GPCR to CARMA3, distinguishing it from PKCθ/ζ and linking the pathway to tumor invasion.

    Evidence Isoform-specific dominant-negative PKC mutants, siRNA of CBM components, NF-κB and invasion assays in ovarian cancer cells

    PMID:17724468

    Open questions at the time
    • Direct PKCα phosphorylation target on the CBM complex not identified
  6. 2008 Medium

    Extended CARMA3-CBM signaling to multiple GPCRs (CXCR2) and tissues, coupling NF-κB to VEGF induction and airway epithelial cytokine production.

    Evidence siRNA/dominant-negative perturbation with VEGF and cytokine readouts in endothelial and airway epithelial cells

    PMID:18757306 PMID:19112107

    Open questions at the time
    • Single-lab pathway placements
    • Direct receptor-to-CARMA3 biochemical bridge not mapped
  7. 2008 Medium

    Identified A20 as a negative regulator that disassembles the CARMA3-BCL10-NEMO complex via deubiquitylation, adding a brake to the pathway.

    Evidence Co-IP complex assembly analysis, deubiquitylation assay, NF-κB reporter

    PMID:18349075

    Open questions at the time
    • Single lab
    • Specific ubiquitin chains targeted on the complex not fully defined
  8. 2010 High

    Revealed cell-type-specific assembly logic—the endothelial CARMA3 signalosome requires β-arrestin 2 rather than PDK1—distinguishing it from the lymphocyte CARMA1 complex downstream of PAR-1.

    Evidence siRNA, Co-IP, PDK1 inhibitor, β-arrestin 2 knockdown, monocyte adhesion assay

    PMID:21041303

    Open questions at the time
    • Structural basis of β-arrestin 2-dependent assembly unresolved
  9. 2010 High

    Demonstrated the CBM signalosome's pathophysiological role in vascular inflammation, with genetic loss protecting against Ang II-driven atherosclerosis and aneurysm.

    Evidence siRNA in endothelial/VSMCs and Bcl10−/− mice in atherosclerosis models

    PMID:20605784

    Open questions at the time
    • Used Bcl10 rather than CARMA3 genetic ablation for the in vivo arm
  10. 2011 High

    Showed CARMA3 also transduces receptor tyrosine kinase (EGFR) signals to IKK/NF-κB, broadening its receptor repertoire beyond GPCRs and linking it to tumor growth.

    Evidence CARMA3-deficient MEFs, siRNA, IKK and NF-κB assays, xenograft tumor model

    PMID:21406399

    Open questions at the time
    • Mechanism coupling EGFR to PKC and CARMA3 not fully defined
  11. 2014 Medium

    Identified DEPDC7 as a CARMA3-specific upstream binding partner required for CBM-dependent but not CARMA1-dependent NF-κB activation.

    Evidence Co-IP and shRNA with receptor-specificity controls

    PMID:25541973

    Open questions at the time
    • Single lab
    • How DEPDC7 modulates complex assembly mechanistically unknown
  12. 2015 High

    Connected CARMA3-driven NF-κB to a transcriptional metastasis program (NF-κB/miR-182/NME2) and to allergic airway inflammation in vivo.

    Evidence ChIP, luciferase, knockdown, metastasis assays; AEC-specific conditional knockout mice in allergic airway model

    PMID:25906011 PMID:26041536

    Open questions at the time
    • Single-lab mechanistic chains
    • Generality of the miR-182 axis across tumor types untested
  13. 2016 High

    Uncovered an NF-κB-independent function: CARMA3 sequesters MAVS to restrain TBK1/IRF3 antiviral signaling, and is proteasomally degraded to release MAVS, positioning it as a switch balancing inflammation versus antiviral response.

    Evidence CARMA3-deficient mice, Co-IP, native PAGE MAVS aggregation, proteasome inhibitor, NF-κB/IRF3 reporters, viral infection model

    PMID:26947079

    Open questions at the time
    • E3 ligase mediating CARMA3 degradation not identified
    • Structural basis of MAVS sequestration unresolved
  14. 2017 Medium

    Confirmed AGTR1-CBM signaling drives breast cancer progression through both ligand-dependent and ligand-independent NF-κB activation.

    Evidence siRNA of CBM components with proliferation/invasion/angiogenesis assays and AGTR1 overexpression models

    PMID:29259013

    Open questions at the time
    • Single lab
    • Mechanism of ligand-independent activation not defined
  15. 2018 Medium

    Placed CARD10 within myeloid development as a direct CEBPE transcriptional target required for normal granulopoiesis, defining an upstream transcriptional control point.

    Evidence ChIP, Cebpe knockout mice, siRNA, gene expression analysis

    PMID:29773596

    Open questions at the time
    • Single lab
    • Whether CARD10's scaffold function or another activity drives granulopoiesis unclear
  16. 2018 Medium

    Identified a physical CARMA3-IP3R interaction controlling calcium release and type 2 immune mediators, an NF-κB-independent role in airway epithelium.

    Evidence Co-IP, CARMA3-deficient AEC mice, intracellular calcium measurement, cytokine ELISA, allergic inflammation model

    PMID:29958012

    Open questions at the time
    • Single lab without reciprocal structural validation
    • Domain mediating IP3R binding unmapped
  17. 2021 High

    Established CARD10 as the first MALT1 substrate in non-hematopoietic cells, with cleavage at R587 forming a built-in negative feedback that limits NF-κB, cytokine, and tumor output.

    Evidence In vitro MALT1 cleavage assay, R587 site-directed mutagenesis, NF-κB reporter, cytokine ELISA, xenograft model

    PMID:33824280

    Open questions at the time
    • Single lab
    • Fate and function of the cleavage fragments not defined
  18. 2022 Medium

    Revealed a mitochondria-localized, scaffold-independent protective role of CARMA3 in liver sinusoidal endothelial cells against immune-mediated injury.

    Evidence CARMA3 knockout mice, subcellular fractionation, Con A hepatitis, cell death and coagulation assays

    PMID:35831018

    Open questions at the time
    • Single lab
    • Molecular mechanism of mitochondrial protection not defined
  19. 2023 Medium

    Linked CARMA3 loss to enhanced VSMC pyroptosis via p38MAPK-coupled ER stress/mitochondrial damage, indicating a protective vascular role distinct from its pro-inflammatory NF-κB function.

    Evidence CARMA3 knockout mice, Ang II osmotic pump model, p38MAPK, ER stress, mitochondrial and pyroptosis assays

    PMID:37030515

    Open questions at the time
    • Single lab
    • Reconciliation with the pro-atherogenic CBM role unaddressed
  20. 2024 Medium

    Showed SHH-PKCα-driven CBM complex formation recruits TRAF6 to trigger caspase-11-dependent myocardial pyroptosis, connecting the scaffold to a programmed cell death pathway.

    Evidence SHH and PKCα inhibitors, Co-IP, TRAF6 recruitment, caspase-11 assays, mouse I/R and H9c2 H/R models

    PMID:39343081

    Open questions at the time
    • Single lab
    • Direct CBM-to-caspase-11 molecular link not fully mapped
  21. 2025 Medium

    Identified a CARMA3-STAT1 interaction that suppresses STAT1 phosphorylation and myofibroblast activation, defining an anti-fibrotic, NF-κB-independent role in cardiac fibroblasts.

    Evidence CARMA3 knockout mice, TAC and Ang II models, Co-IP, proteomics, STAT1 phosphorylation assays

    PMID:41053092

    Open questions at the time
    • Single lab without reciprocal validation
    • Mechanism by which CARMA3 inhibits STAT1 phosphorylation unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CARMA3 partitions between its canonical CBM/NF-κB scaffolding role and its growing set of NF-κB-independent activities (MAVS sequestration, IP3R-calcium control, mitochondrial protection, STAT1 inhibition) remains unresolved.
  • No structural model of the assembled CBM signalosome
  • Domains and post-translational modifications governing the switch between scaffold and non-scaffold functions undefined
  • No human disease mutation linkage established in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005739 mitochondrion 1 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 2
Partners
BCL10DEPDC7IKBKGITPR1MALT1MAVSSTAT1TRAF6
Complex memberships
CBM (CARMA3-BCL10-MALT1) signalosomeIKK complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CARD10/BIMP1 (CARMA3) physically binds BCL10 via its CARD domain and forms a ternary complex with BCL10 and MALT1 (with BCL10 bridging the BIMP1/MALT1 interaction). This complex activates NF-κB through IκB kinases, and a dominant-negative BIMP1 mutant inhibits NF-κB activation by anti-CD3 ligation, phorbol ester, and PKC expression, placing CARD10 upstream of IKK in the PKC-to-NF-κB signaling axis. Co-immunoprecipitation, dominant-negative mutant expression, NF-κB reporter assays The Journal of biological chemistry High 11387339
2001 CARD10 is a MAGUK/CARD family scaffold protein that binds BCL10 through its N-terminal CARD domain and activates NF-κB when expressed in cells, proposed to organize a BCL10 signaling complex at plasma membranes. Co-immunoprecipitation, NF-κB reporter assay, domain mapping The Journal of biological chemistry High 11259443
2004 CARMA3 physically associates with IKKγ/NEMO in non-lymphoid cells. CARMA3 participates in a large inducible complex containing IKKγ/NEMO, BCL10, and IKKα/β kinases. Expression of the NEMO-binding region of CARMA3 acts as a dominant negative, suppressing BCL10-mediated NF-κB activation, establishing direct physical and functional linkage between CARMA3 and the IKK complex. Co-immunoprecipitation, dominant-negative expression, NF-κB reporter assay The Journal of biological chemistry High 15184390
2006 CARMA3 is required for angiotensin II (Ang II) receptor (type 1 GPCR)-induced NF-κB activation in hepatocytes. CARMA3, BCL10, and MALT1 form the CBM complex downstream of Ang II receptor; blocking any component via dominant-negative mutants, RNAi, or gene targeting abolishes Ang II-dependent NF-κB activation. The pathway activates NF-κB through ubiquitination of IKKγ/NEMO. Dominant-negative mutants, RNAi, gene targeting (Bcl10−/− mice), NF-κB activation assays, in vivo cytokine production assay Proceedings of the National Academy of Sciences of the United States of America High 17101977
2007 CARMA3 is required for GPCR-induced IKK activation and NF-κB signaling. CARMA3-deficient mice generated by gene targeting show abrogated GPCR-induced NF-κB activation; CARMA3 physically associates with NEMO/IKKγ and induces polyubiquitination of NEMO-associated protein(s), likely by linking NEMO to TRAF6. CARMA3 deficiency impairs IKK kinase activity despite normal IKKα/β phosphorylation. CARMA3 knockout mice (gene targeting), Co-immunoprecipitation, ubiquitination assay, IKK kinase assay Genes & development High 17438001
2007 PKCα links LPA receptor (GPCR) to CARMA3 for NF-κB activation and uPA upregulation in ovarian cancer cells. LPA stimulation activates PKCα and induces Ras-PKCα interaction; dominant-negative PKCα, but not PKCθ or PKCζ DN mutants, blocks LPA-induced NF-κB activation. Dominant-negative CARMA3 or siRNA silencing of CARMA3/BCL10/MALT1 abolishes LPA-induced NF-κB activation and invasion. Dominant-negative mutants, siRNA knockdown, NF-κB reporter assay, Co-immunoprecipitation, invasion assay Oncogene High 17724468
2008 CXCL8/IL8 acting on CXCR2 activates NF-κB and upregulates VEGF mRNA and protein in endothelial cells through the CBM complex (CARMA3/BCL10/MALT1); this is independent of HIF1α. Knockdown of CBM components blocks CXCL8-induced VEGF upregulation and autocrine VEGFR2 activation. siRNA knockdown, Western blot, NF-κB reporter assay, VEGF mRNA quantification The Journal of biological chemistry Medium 19112107
2008 A20 negatively regulates CARMA3/BCL10/IKKγ(NEMO)-mediated NF-κB activation via its deubiquitylation activity. A20 perturbs assembly of the CARMA3-BCL10-IKKγ/NEMO complex, thereby suppressing NF-κB activation in non-lymphoid cells. Co-immunoprecipitation, deubiquitylation assay, NF-κB reporter assay, complex assembly analysis Journal of cell science Medium 18349075
2008 CARMA3 is specifically expressed in human airway bronchial epithelial cells and mediates LPA-stimulated NF-κB activation and cytokine production (TSLP, CCL20) in these cells. Inhibition of CARMA3 activity reduces LPA-mediated NF-κB activity and TSLP/CCL20 production. Dominant-negative expression, NF-κB reporter assay, cytokine ELISA, expression analysis American journal of respiratory cell and molecular biology Medium 18757306
2009 The CXCR4/SDF-1α GPCR activates NF-κB and promotes OSCC invasion through the CBM complex (CARMA3/BCL10/MALT1). Knockdown of CBM components inhibits SDF-1α-induced IκBα phosphorylation and degradation (but not TNFα-induced IKK activation). Novel and atypical (but not classical) PKCs activate IKK through CXCR4. Lentiviral shRNA knockdown, Western blot (IκBα phosphorylation), EMSA, invasion assay International journal of oral science Medium 20695076
2010 Thrombin acting on PAR-1 (a GPCR) on endothelial cells uses the CARMA3·BCL10·MALT1 signalosome to link PKC activation to IKK stimulation and NF-κB-dependent ICAM-1/VCAM-1 expression, driving monocyte adhesion to endothelium. Unlike the lymphocyte CARMA1 signalosome, the CARMA3 endothelial signalosome does not require PDK1 but instead depends on β-arrestin 2 for assembly. siRNA knockdown, Co-immunoprecipitation, NF-κB reporter assay, monocyte adhesion assay, PDK1 inhibitor and β-arrestin 2 knockdown The Journal of biological chemistry High 21041303
2010 The CARMA3-BCL10-MALT1 signalosome mediates angiotensin II type 1 receptor-induced NF-κB activation in endothelial and vascular smooth muscle cells, promoting pro-inflammatory vascular signaling and atherogenesis. Bcl10-deficient mice are protected from Ang II-dependent atherosclerosis and aortic aneurysms. siRNA knockdown, Bcl10−/− mice (in vivo atherosclerosis model), NF-κB activation assays The Journal of biological chemistry High 20605784
2011 CARMA3 is required for EGF receptor (RTK)-induced IKK activation and NF-κB signaling. CARMA3 deficiency impairs EGF-induced IκBα phosphorylation and NF-κB activation. CARMA3 and BCL10 contribute to EGFR-associated proliferation, survival, migration, invasion, and tumor growth in vivo. CARMA3-deficient MEFs, siRNA knockdown, IKK assay, NF-κB reporter assay, xenograft tumor model Cancer research High 21406399
2014 DEPDC7 (DEP domain-containing protein) binds to CARMA3 as a cellular binding partner. shRNA-mediated abrogation of DEPDC7 impairs NF-κB activation following GPCR stimulation or stimuli requiring CARMA3, but not CARMA1, establishing DEPDC7 as a CARMA3-specific upstream component of the CBM complex. Co-immunoprecipitation, shRNA knockdown, NF-κB reporter assay PloS one Medium 25541973
2015 CARMA3 promotes lung cancer cell motility by reducing NME2 expression through the NF-κB/miR-182 pathway. Mechanistically, CARMA3 activates NF-κB, which drives miR-182 transcription (confirmed by ChIP and luciferase reporter assay), and miR-182 then suppresses NME2, a metastasis suppressor, thereby increasing cancer stemness and metastasis. ChIP assay, luciferase reporter assay, siRNA/shRNA knockdown, in vitro and in vivo metastasis assays American journal of respiratory and critical care medicine Medium 25906011
2015 CARMA3 is required for GPCR ligand (LPA, ATP, Alternaria, house dust mite)-induced NF-κB activation and proasthmatic mediator production in airway epithelial cells (AECs). CARMA3-deficient AECs have reduced allergic inflammation. Mice with CARMA3-deficient AECs have reduced airway eosinophilia, cytokine production, and impaired dendritic cell maturation in a murine model of allergic airway inflammation. CARMA3 conditional KO mice (AEC-specific), NF-κB reporter assay, cytokine ELISA, flow cytometry, antigen processing assay Journal of immunology High 26041536
2016 CARMA3 positively regulates MAVS-induced NF-κB activation during RNA virus infection. Conversely, CARMA3 sequesters MAVS from forming high-molecular-weight aggregates, suppressing TBK1/IRF3 activation. After NF-κB activation, CARMA3 is degraded in a proteasome-dependent manner, releasing MAVS to activate IRF3. CARMA3-deficient mice show reduced inflammation and stronger viral clearance. CARMA3-deficient mice, Co-immunoprecipitation, native PAGE (MAVS aggregate detection), proteasome inhibitor assay, NF-κB/IRF3 reporter assays, in vivo viral infection model Cell reports High 26947079
2017 AGTR1 (angiotensin II receptor) overexpression in breast cancer drives NF-κB activation via the CARMA3-BCL10-MALT1 (CBM) signalosome, promoting proliferation, migration, invasion, and tumor angiogenesis. Both ligand-dependent and ligand-independent AGTR1-mediated NF-κB activation requires the CBM triad. siRNA knockdown of CBM components, NF-κB reporter assay, proliferation/migration/invasion assays, endothelial angiogenesis assay, AGTR1 overexpression models Cancer research Medium 29259013
2018 CARD10 is a direct transcriptional target of the myeloid transcription factor CEBPE. CEBPE binds to regulatory elements upstream of the murine Card10 locus (confirmed by ChIP), and CARD10 expression is significantly reduced in Cebpe knockout mice. Silencing Card10 impairs granulopoiesis, affecting expression of genes involved in myeloid cell development and function. ChIP assay, Cebpe knockout mice, siRNA knockdown in human cell line and murine primary cells, gene expression analysis Haematologica Medium 29773596
2018 CARMA3 mediates Alternaria alternata-induced allergic airway inflammation in AECs. CARMA3 interacts with inositol 1,4,5-trisphosphate receptors (IP3Rs) in AECs, and inhibition of CARMA3 signaling reduces A. alternata-induced intracellular calcium release, reducing IL-33, IL-25, and type 2 immune responses. Co-immunoprecipitation (CARMA3-IP3R interaction), CARMA3-deficient AEC mice, intracellular calcium measurement, cytokine ELISA, in vivo allergic inflammation model American journal of respiratory cell and molecular biology Medium 29958012
2021 CARD10 is the first identified MALT1 substrate in non-hematopoietic cells. MALT1 cleaves CARD10 at R587, and this cleavage dampens CARD10's capacity to activate NF-κB. Preventing CARD10 cleavage increases basal IL-6 and extracellular matrix components in vitro and leads to increased tumor growth in a mouse xenograft model, indicating that MALT1-mediated CARD10 cleavage is a built-in negative regulatory mechanism. In vitro MALT1 cleavage assay, site-directed mutagenesis (R587 cleavage site), NF-κB reporter assay, cytokine ELISA, mouse xenograft tumor model Oncogenesis High 33824280
2022 CARMA3 localizes at mitochondria in liver sinusoidal endothelial cells (LSECs). In CARMA3-deficient mice, Con A-induced liver injury is exacerbated, with more LSEC damage, mitochondrial damage, and coagulation. In vitro, CARMA3-deficient LSECs show increased mitochondrial damage and cell death upon Con A treatment, revealing a mitochondria-protective role of CARMA3 in LSECs distinct from its NF-κB scaffolding function. CARMA3 knockout mice, subcellular fractionation/localization of CARMA3 to mitochondria, Con A hepatitis model, cell death assay, coagulation assay Journal of immunology Medium 35831018
2023 CARMA3 deficiency exacerbates Ang II-induced abdominal aortic aneurysm (AAA) formation, increased inflammatory cytokines, MMP expression, and VSMC death. Mechanistically, CARMA3 deficiency activates the p38MAPK pathway, enhancing the interaction between ER stress and mitochondrial damage, ultimately promoting VSMC pyroptosis. CARMA3 knockout mice, Ang II osmotic pump model, p38MAPK pathway analysis, ER stress markers, mitochondrial damage assays, pyroptosis assays The Canadian journal of cardiology Medium 37030515
2024 Sonic hedgehog (SHH) signaling promotes myocardial pyroptosis after I/R injury via PKCα-mediated CARD10-BCL10-MALT1 (CBM) complex formation. SHH activation increases PKCα levels; PKCα inhibition attenuates CBM complex formation. Disruption of the CBM complex prevents MALT1 from recruiting TRAF6, which is required to trigger caspase-11-dependent pyroptosis. SHH pathway inhibitors, PKCα inhibitor, Co-immunoprecipitation (CBM complex), TRAF6 recruitment assay, caspase-11 activation assay, mouse I/R model and H9c2 H/R model European journal of pharmacology Medium 39343081
2025 CARMA3 suppresses myofibroblast activation in cardiac fibroblasts by inhibiting STAT1 phosphorylation. An interaction between CARMA3 and STAT1 was detected in response to pressure overload. CARMA3-knockout mice subjected to TAC or Ang II treatment show increased cardiac fibrosis, myofibroblast differentiation, and mitochondrial damage; proteomic analysis identified elevated STAT1 in CARMA3-KO cardiac fibroblasts. CARMA3 knockout mice, TAC and Ang II models, Co-immunoprecipitation (CARMA3-STAT1), proteomic analysis, flow cytometry, STAT1 phosphorylation assay Cell death discovery Medium 41053092

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 CXCL8/IL8 stimulates vascular endothelial growth factor (VEGF) expression and the autocrine activation of VEGFR2 in endothelial cells by activating NFkappaB through the CBM (Carma3/Bcl10/Malt1) complex. The Journal of biological chemistry 335 19112107
2001 Bimp1, a MAGUK family member linking protein kinase C activation to Bcl10-mediated NF-kappaB induction. The Journal of biological chemistry 154 11387339
2006 CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells. Proceedings of the National Academy of Sciences of the United States of America 150 17101977
2001 Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B. The Journal of biological chemistry 131 11259443
2007 CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-{kappa}B activation. Genes & development 109 17438001
2012 microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-κB by targeting CARD10 and COPS8 in gastric cancer. Molecular cancer 86 22992343
2009 CXCL12/SDF-1 alpha activates NF-kappaB and promotes oral cancer invasion through the Carma3/Bcl10/Malt1 complex. International journal of oral science 85 20695076
2011 CARMA3 is crucial for EGFR-Induced activation of NF-κB and tumor progression. Cancer research 76 21406399
2017 The CARMA3-Bcl10-MALT1 Signalosome Drives NFκB Activation and Promotes Aggressiveness in Angiotensin II Receptor-Positive Breast Cancer. Cancer research 74 29259013
2011 Genome-wide association studies in Asians confirm the involvement of ATOH7 and TGFBR3, and further identify CARD10 as a novel locus influencing optic disc area. Human molecular genetics 70 21307088
2010 Thrombin-dependent NF-{kappa}B activation and monocyte/endothelial adhesion are mediated by the CARMA3·Bcl10·MALT1 signalosome. The Journal of biological chemistry 69 21041303
2007 Protein kinase C alpha-CARMA3 signaling axis links Ras to NF-kappa B for lysophosphatidic acid-induced urokinase plasminogen activator expression in ovarian cancer cells. Oncogene 67 17724468
2010 The CARMA3-Bcl10-MALT1 signalosome promotes angiotensin II-dependent vascular inflammation and atherogenesis. The Journal of biological chemistry 66 20605784
2004 Physical and functional interaction of CARMA1 and CARMA3 with Ikappa kinase gamma-NFkappaB essential modulator. The Journal of biological chemistry 62 15184390
2014 MicroRNA-195 inhibits colorectal cancer cell proliferation, colony-formation and invasion through targeting CARMA3. Molecular medicine reports 46 24787958
2014 Lipopolysaccharide-induced microRNA-146a targets CARD10 and regulates angiogenesis in human umbilical vein endothelial cells. Toxicological sciences : an official journal of the Society of Toxicology 41 24863965
2008 CARMA3 mediates lysophosphatidic acid-stimulated cytokine secretion by bronchial epithelial cells. American journal of respiratory cell and molecular biology 36 18757306
2015 MicroRNA-24 upregulation inhibits proliferation, metastasis and induces apoptosis in bladder cancer cells by targeting CARMA3. International journal of oncology 35 26252200
2008 A20 is a negative regulator of BCL10- and CARMA3-mediated activation of NF-kappaB. Journal of cell science 35 18349075
2015 CARMA3 Represses Metastasis Suppressor NME2 to Promote Lung Cancer Stemness and Metastasis. American journal of respiratory and critical care medicine 30 25906011
2012 Overexpression of CARMA3 in non-small-cell lung cancer is linked for tumor progression. PloS one 29 22615840
2012 CARMA3 is overexpressed in colon cancer and regulates NF-κB activity and cyclin D1 expression. Biochemical and biophysical research communications 29 22884800
2019 The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer. Cancer gene therapy 24 30723269
2018 Caspase recruitment domain (CARD) family (CARD9, CARD10, CARD11, CARD14 and CARD15) are increased during active inflammation in patients with inflammatory bowel disease. Journal of inflammation (London, England) 24 30008619
2018 CARMA3 Is a Critical Mediator of G Protein-Coupled Receptor and Receptor Tyrosine Kinase-Driven Solid Tumor Pathogenesis. Frontiers in immunology 24 30158935
2016 CARMA3 Is a Host Factor Regulating the Balance of Inflammatory and Antiviral Responses against Viral Infection. Cell reports 23 26947079
2013 CARMA3 overexpression accelerates cell proliferation and inhibits paclitaxel-induced apoptosis through NF-κB regulation in breast cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 23708960
2019 CARMA3: Scaffold Protein Involved in NF-κB Signaling. Frontiers in immunology 22 30814996
2015 CARMA3 Is Critical for the Initiation of Allergic Airway Inflammation. Journal of immunology (Baltimore, Md. : 1950) 22 26041536
2014 The Dishevelled, EGL-10 and pleckstrin (DEP) domain-containing protein DEPDC7 binds to CARMA2 and CARMA3 proteins, and regulates NF-κB activation. PloS one 22 25541973
2010 CARMA3: A novel scaffold protein in regulation of NF-κB activation and diseases. World journal of biological chemistry 22 21537470
2013 CARMA3 is overexpressed in human glioma and promotes cell invasion through MMP9 regulation in A172 cell line. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 21 23893382
2014 Overexpression of CARMA3 is associated with advanced tumor stage, cell cycle progression, and cisplatin resistance in human epithelial ovarian cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20 24833094
2018 CARMA3 Mediates Allergic Lung Inflammation in Response to Alternaria alternata. American journal of respiratory cell and molecular biology 18 29958012
2015 CARMA3 regulates the invasion, migration, and apoptosis of non-small cell lung cancer cells by activating NF-кB and suppressing the P38 MAPK signaling pathway. Experimental and molecular pathology 18 26526492
2021 MicroRNA‑16‑5p/BIMP1/NF‑κB axis regulates autophagy to exert a tumor‑suppressive effect on bladder cancer. Molecular medicine reports 15 34132358
2019 CARD10 promotes the progression of renal cell carcinoma by regulating the NF‑κB signaling pathway. Molecular medicine reports 15 31939627
2019 CARMA3/NF-κB signaling contributes to tumorigenesis of hepatocellular carcinoma and is inhibited by sodium aescinate. World journal of gastroenterology 14 31576094
2021 CARD10 cleavage by MALT1 restricts lung carcinoma growth in vivo. Oncogenesis 13 33824280
2018 Association of CARD10 rs6000782 and TNF rs1799724 variants with paediatric-onset autoimmune hepatitis. Journal of advanced research 13 30581618
2014 Clinical significance and biological roles of CARMA3 in human bladder carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 13 24443255
2021 CARMA3 Promotes Colorectal Cancer Cell Motility and Cancer Stemness via YAP-Mediated NF-κB Activation. Cancers 12 34885061
2016 Rare variants in optic disc area gene CARD10 enriched in primary open-angle glaucoma. Molecular genetics & genomic medicine 12 27896285
2020 miR-146a regulates inflammation and development in patients with abdominal aortic aneurysms by targeting CARD10. International angiology : a journal of the International Union of Angiology 11 32138469
2021 Staphylococcus aureus Induces IFN-β Production via a CARMA3-Independent Mechanism. Pathogens (Basel, Switzerland) 10 33806598
2019 Silencing of CARMA3 inhibits bladder cancer cell migration and invasion via deactivating β-catenin signaling pathway. OncoTargets and therapy 10 31496734
2021 CARMA3 Transcriptional Regulation of STMN1 by NF-κB Promotes Renal Cell Carcinoma Proliferation and Invasion. Technology in cancer research & treatment 9 34190011
2015 Lack of association between the CARD10 rs6000782 polymorphism and type 1 autoimmune hepatitis in a Japanese population. BMC research notes 9 26652023
2014 CARMA3 is upregulated in human pancreatic carcinoma, and its depletion inhibits tumor proliferation, migration, and invasion. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 9 24633921
2023 CARMA3 Deficiency Aggravates Angiotensin II-Induced Abdominal Aortic Aneurysm Development Interacting Between Endoplasmic Reticulum and Mitochondria. The Canadian journal of cardiology 8 37030515
2018 CARD10, a CEBPE target involved in granulocytic differentiation. Haematologica 8 29773596
2018 Analysis of CARD10 and CARD11 somatic mutations in patients with ovarian endometriosis. Oncology letters 8 29928437
2024 Sonic hedgehog signaling facilitates pyroptosis in mouse heart following ischemia/reperfusion via enhancing the formation of CARD10-BCL10-MALT1 complex. European journal of pharmacology 6 39343081
2022 CARMA3: A potential therapeutic target in non-cancer diseases. Frontiers in immunology 6 36618379
2021 Deficiency of CARMA3 attenuates the development of bleomycin induced pulmonary fibrosis. Biochemical and biophysical research communications 5 34656852
2024 CARMA3 Drives NF-κB Activation and Promotes Intervertebral Disc Degeneration: Involvement of CARMA3-BCL10-MALT1 Signalosome. Inflammation 3 38607566
2017 Lack of association between CARD10/CARMA3 tag SNPs and psoriasis vulgaris in the southern Chinese population. Genetics and molecular research : GMR 3 28301668
2025 The role of CARMA3 in regulating fibrosis to prevent hypertrophic cardiomyopathy. Cell death discovery 2 41053092
2022 Carma3 Protects from Liver Injury by Preserving Mitochondrial Integrity in Liver Sinusoidal Endothelial Cells. Journal of immunology (Baltimore, Md. : 1950) 2 35831018
2025 Disrupting CARMA3 Signaling with Triptolide Reverses Sorafenib Resistance in Hepatocellular Carcinoma. International journal of medical sciences 0 41209553
2023 [Retracted] MicroRNA‑24 upregulation inhibits proliferation, metastasis and induces apoptosis in bladder cancer cells by targeting CARMA3. International journal of oncology 0 37083072

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