Affinage

BCL10

B-cell lymphoma/leukemia 10 · UniProt O95999

Length
233 aa
Mass
26.3 kDa
Annotated
2026-04-28
100 papers in source corpus 43 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCL10 is a CARD domain-containing adaptor protein that serves as the central scaffold in the CARMA–BCL10–MALT1 (CBM) signalosome, coupling antigen receptors, Fc receptors, GPCRs, and TLR4 to canonical NF-κB activation in both immune and non-immune cells (PMID:11163238, PMID:17179215, PMID:18252714). Upon receptor engagement, PKC-phosphorylated CARMA1 (or CARMA3) nucleates cooperative BCL10 CARD filament polymerization; these filaments recruit MALT1, TRAF6, and IKK via K63-linked polyubiquitination of BCL10 (at K31/K63) and NEMO, activating the IKK complex (PMID:24074955, PMID:29382759, PMID:14695475, PMID:18287044). Signal amplitude and duration are tightly regulated by negative-feedback phosphorylation (IKKβ, CaMKII) that promotes BCL10 ubiquitination and lysosomal degradation through NEDD4/Itch, cIAP2, and other E3 ligases, while calcineurin-mediated dephosphorylation sustains CBM assembly (PMID:16818229, PMID:17052756, PMID:15082780, PMID:16395405, PMID:21199863). Independent of NF-κB, BCL10 regulates actin polymerization and phagocytic cup formation by delivering OCRL phosphatase via AP1/EpsinR vesicles, a function governed by Ser138 phosphorylation (PMID:17371994, PMID:23153494).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Identification of BCL10 as a CARD-domain protein that activates NF-κB and apoptosis established the gene's dual signaling capacity and mapped functional domains: the CARD mediates NF-κB activation while the C-terminus is required for apoptosis and suppresses transformation.

    Evidence Overexpression and truncation mutagenesis in 293/MCF7 cells with NF-κB reporter, apoptosis, and transformation assays

    PMID:10319863 PMID:9989495

    Open questions at the time
    • Physiological upstream signals unknown
    • Endogenous binding partners not identified
    • Mechanism linking CARD to NF-κB not defined
  2. 2001 High

    Knockout mice and interaction studies revealed that BCL10 is specifically required for antigen receptor-to-NF-κB signaling in lymphocytes, forms a complex with MALT1 to synergistically activate IKK, and is scaffolded by CARMA1 via CARD–CARD interactions — defining the core CBM signalosome.

    Evidence Bcl10−/− mice with lymphocyte stimulation assays; reciprocal Co-IP of BCL10–MALT1 and CARMA1–BCL10; NF-κB and IKK activation assays

    PMID:11163238 PMID:11262391 PMID:11356195

    Open questions at the time
    • Biochemical mechanism connecting CBM to IKK activation unknown
    • Structural basis of CARD–CARD interaction undefined
    • Roles outside adaptive immunity not tested
  3. 2003 High

    The mechanism linking BCL10 to IKK was resolved: BCL10 promotes K63-linked polyubiquitination of NEMO via MALT1 paracaspase and UBC13, and this ubiquitination is required for NF-κB activation, establishing the ubiquitin-dependent signaling output of the CBM complex.

    Evidence In vitro ubiquitination assays, NEMO ubiquitination-deficient mutants, MALT1/UBC13 RNAi

    PMID:14695475

    Open questions at the time
    • Ubiquitination sites on BCL10 itself not mapped
    • E3 ligase for BCL10 ubiquitination not identified
    • Higher-order assembly mechanism unknown
  4. 2004 High

    Signal termination mechanisms were identified: NEDD4 and Itch ubiquitinate BCL10 for lysosomal degradation after T-cell activation, and cIAP2 targets BCL10 for proteasomal degradation — explaining how NF-κB is attenuated and why the cIAP2-MALT1 fusion stabilizes BCL10 in MALT lymphoma.

    Evidence Proteasome/lysosome inhibitors, ubiquitin ligase overexpression, in vitro ubiquitination with cIAP2

    PMID:15082780 PMID:16395405

    Open questions at the time
    • Specific ubiquitin chain types on BCL10 for degradation not determined
    • Relative contributions of lysosomal vs. proteasomal pathways in vivo unclear
  5. 2006 High

    Multiple negative-feedback phosphorylation events were mapped: IKKβ phosphorylates the BCL10 C-terminus to disrupt BCL10–MALT1 association, while CaMKII phosphorylates Ser138 to attenuate NF-κB — revealing phosphorylation as a multi-layered signal termination mechanism.

    Evidence In vitro kinase assays, phospho-site mutagenesis (S138A), primary T cell cytokine assays, CaMKII inhibitors/siRNA

    PMID:16818229 PMID:17052756

    Open questions at the time
    • Full phosphorylation map of BCL10 not determined
    • Phosphatases reversing these modifications not yet identified
  6. 2006 High

    BCL10's role was extended beyond adaptive immunity: Bcl10−/− cells revealed that BCL10–MALT1 mediates NF-κB activation downstream of FcεRI in mast cells and GPCRs (LPA, endothelin-1) in non-immune cells, while remaining dispensable for degranulation, MAPK, and Akt pathways.

    Evidence Bcl10−/− and Malt1−/− mast cells, Bcl10−/− MEFs, multiple receptor agonists with pathway-specific readouts

    PMID:16432253 PMID:17095601 PMID:17179215

    Open questions at the time
    • Upstream adaptor connecting GPCRs to BCL10 not defined
    • Whether CARMA3 is the obligate scaffold in all non-immune contexts not established
  7. 2007 High

    An NF-κB-independent function was discovered: Ser138 phosphorylation of BCL10 selectively controls TCR- and FcγR-induced actin polymerization; BCL10 knockdown impairs F-actin formation, cell spreading, and phagocytosis independently of CARMA1, separating BCL10's cytoskeletal role from its NF-κB role.

    Evidence siRNA, S138A mutagenesis, F-actin imaging, phagocytosis assays in T cells and monocytes

    PMID:17371994

    Open questions at the time
    • Downstream effectors linking BCL10 phospho-S138 to actin not identified
    • Structural basis for NF-κB vs. actin pathway bifurcation unknown
  8. 2008 High

    BCL10's own ubiquitination sites were mapped to K31 and K63 (K63-linked chains); ubiquitinated BCL10 directly recruits NEMO via NEMO's ubiquitin-binding domain, and mutation of these sites blocks NF-κB without disrupting CBM assembly, ordering ubiquitination downstream of complex formation.

    Evidence Ubiquitination site mapping by mutagenesis (K31R/K63R), NEMO binding assay, NF-κB reporter

    PMID:18287044

    Open questions at the time
    • E3 ligase catalyzing K63-linked ubiquitination of BCL10 at K31/K63 not identified in this study
    • Role of other ubiquitin chain types on BCL10 unclear
  9. 2011 High

    Calcineurin was identified as a phosphatase that dephosphorylates BCL10 to sustain CBM complex assembly, explaining how immunosuppressants cyclosporin A/FK506 inhibit NF-κB partly through BCL10 hyperphosphorylation.

    Evidence In vitro/in vivo phosphatase assay, cyclosporin A/FK506 treatment, calcineurin siRNA

    PMID:21199863

    Open questions at the time
    • Specific BCL10 residues dephosphorylated by calcineurin not mapped
    • Relative importance vs. CaMKII/IKKβ phosphorylation in vivo not quantified
  10. 2012 High

    The NF-κB-independent actin-regulatory mechanism was molecularly defined: BCL10 forms a complex with clathrin adaptors AP1 and EpsinR to deliver OCRL phosphatase to phagocytic cups, controlling PI(4,5)P2 turnover and Rac1/PI3K activation during phagocytosis.

    Evidence siRNA depletion, live-cell imaging, Co-IP of BCL10 with AP1/EpsinR, phosphoinositide analysis in macrophages

    PMID:23153494

    Open questions at the time
    • Whether BCL10–AP1/EpsinR complexes function outside phagocytosis unknown
    • Structural basis of BCL10–clathrin adaptor interaction not resolved
  11. 2013 High

    Structural reconstitution revealed the CBM signalosome as a helical filamentous assembly: substoichiometric CARMA1 nucleates cooperative BCL10 CARD filament polymerization; crystal/NMR/EM structures defined CARD–CARD interfaces essential for filament formation and MALT1 recruitment.

    Evidence In vitro reconstitution, crystallography, NMR, cryo-EM, structure-guided mutagenesis with NF-κB reporter

    PMID:24074955

    Open questions at the time
    • Full-length BCL10 structure not determined
    • How MALT1 binds the filament at atomic resolution not resolved
  12. 2018 High

    Higher-resolution cryo-EM of BCL10 CARD filaments and imaging of CARMA1-nucleated star-shaped networks showed that MALT1 cooperatively binds and dimerizes on BCL10 filaments, while TRAF6 decorates CBM filaments to form higher-order signaling assemblies — completing the structural model of the signalosome.

    Evidence Cryo-EM at 4.0 Å, time-lapse confocal, in vitro polymerization

    PMID:29382759

    Open questions at the time
    • Atomic-resolution structure of full CBM including MALT1 and TRAF6 not achieved
    • How filament disassembly is regulated structurally unknown
  13. 2019 High

    BCL10 was shown to be essential for regulatory T cell development and suppressive function; Treg-specific BCL10 deletion causes lethal autoimmunity with conversion of Tregs to IFNγ-producing proinflammatory cells, establishing a non-redundant role in immune tolerance.

    Evidence Conditional knockout (Bcl10fl/fl Foxp3cre), adoptive transfer, gene expression profiling

    PMID:31595055

    Open questions at the time
    • Whether BCL10 acts through NF-κB alone or also actin remodeling in Tregs not dissected
    • Downstream NF-κB target genes in Tregs not identified
  14. 2021 High

    New E3 ligases and deubiquitinases were identified: TRIM41 catalyzes K63-linked polyubiquitination of BCL10 to activate NF-κB and TBK1-IRF3 in innate antiviral responses, while USP12 stabilizes BCL10 specifically in CD4+ T cells — expanding the regulatory ubiquitin code on BCL10.

    Evidence In vitro/in vivo ubiquitination assays, TRIM41−/− macrophages with viral infection, USP12−/− mice with T cell assays

    PMID:33640899 PMID:33941870

    Open questions at the time
    • Whether TRIM41 and previously identified E3s act on overlapping or distinct BCL10 lysine residues unknown
    • Full deubiquitinase landscape for BCL10 not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the atomic-resolution structure of the complete CBM signalosome with MALT1 and TRAF6 integrated; the molecular basis for bifurcation between NF-κB and actin-regulatory pathways at BCL10; and the cell-type-specific combinatorial ubiquitin code that tunes BCL10 signal amplitude.
  • Full atomic structure of BCL10 in complex with MALT1 and TRAF6 not available
  • Mechanism by which phospho-S138 switches BCL10 from NF-κB to actin pathway not resolved
  • Comprehensive in vivo mapping of BCL10 post-translational modifications across cell types lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0005198 structural molecule activity 2
Localization
GO:0005829 cytosol 4 GO:0005634 nucleus 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 10 R-HSA-168256 Immune System 5 R-HSA-5357801 Programmed Cell Death 2
Partners
CARD10CARD11MALT1NEMOOCRLTRAF6TRIM41USP9X
Complex memberships
BCL10-AP1-EpsinRCARMA3-BCL10-MALT1CBM signalosome (CARMA1-BCL10-MALT1)

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 BCL10 encodes a protein with an N-terminal caspase recruitment domain (CARD); wild-type BCL10 activates NF-κB and induces apoptosis, while C-terminal truncation mutants activate NF-κB but lose pro-apoptotic activity and gain transforming activity, mapping functional domains to specific regions. Overexpression in 293/MCF7 cells, mutational analysis, transformation assays Cell High 10319863 9989495
2001 BCL10 is required for antigen receptor (TCR/BCR)-induced NF-κB activation in lymphocytes; bcl10-/- mice show severe immunodeficiency with absent antigen receptor-induced NF-κB activation, while MAPK, AP-1, Ca2+ signaling remain intact, placing BCL10 specifically in the antigen-receptor-to-NF-κB pathway. Knockout mouse model, lymphocyte stimulation assays, NF-κB activation assays Cell High 11163238
2001 BCL10 forms a strong complex with MALT1; BCL10 mediates oligomerization and activation of the MALT1 caspase-like domain, and together BCL10 and MALT1 synergistically activate NF-κB through the IKK complex. Co-immunoprecipitation, NF-κB reporter assays, overexpression The Journal of biological chemistry High 11262391
2001 CARMA1 (Carma1) binds BCL10 via its CARD domain, induces translocation of BCL10 from the cytoplasm into perinuclear structures, causes phosphorylation of BCL10, and activates NF-κB; CARMA1 is a scaffold for the BCL10-dependent NF-κB signaling pathway in T cells. Co-immunoprecipitation, fluorescence microscopy, phosphorylation assay, NF-κB reporter assay FEBS letters High 11356195
2003 BCL10 activates NF-κB through promoting lysine-63-linked polyubiquitination of NEMO (IKKγ); paracaspase (MALT1) and the ubiquitin-conjugating enzyme UBC13 are both required for BCL10-induced NEMO ubiquitination; a NEMO mutant unable to be ubiquitinated blocks BCL10-induced NF-κB activation. Ubiquitination assay, mutant NEMO rescue, siRNA knockdown of MALT1 and UBC13 Nature High 14695475
2003 Bcl10 deficiency impairs development of follicular, marginal zone, and B1 B cells; Bcl10-/- follicular and marginal zone B cells fail to proliferate normally, and marginal zone B cells fail to activate NF-κB after LPS stimulation, establishing Bcl10 as essential for all mature B cell subset development. Knockout mouse model, B-cell subset analysis, proliferation assays, NF-κB activation assays Nature immunology High 12910267
2004 T-cell activation via PKC or TCR/CD28 induces Bcl10 degradation through the lysosomal pathway (not proteasome); HECT domain ubiquitin ligases NEDD4 and Itch promote ubiquitination and lysosomal degradation of Bcl10, selectively terminating IKK/NF-κB signaling as a negative feedback mechanism. Western blot, proteasome inhibitors, lysosomal localization, ubiquitin ligase overexpression Molecular and cellular biology High 15082780
2006 cIAP2 functions as an E3 ubiquitin ligase that ubiquitinates BCL10 and targets it for degradation, thereby inhibiting antigen receptor-mediated NF-κB activation; the cIAP2-MALT1 fusion protein lacks E3 activity, stabilizing BCL10 and promoting NF-κB in MALT lymphomas. In vitro ubiquitination assay, co-immunoprecipitation, BCL10 protein level measurement The Journal of clinical investigation High 16395405
2006 IKKβ is required for initial CBM complex formation and subsequently phosphorylates Bcl10 at the C terminus, interfering with Bcl10/MALT1 association and Bcl10-mediated IKKγ ubiquitination; IKKβ-mediated phosphorylation of Bcl10 thus exerts negative feedback on T cell NF-κB activation. Kinase assay, co-immunoprecipitation, phosphorylation site mutants, primary T cell cytokine assays Molecular cell High 16818229
2006 Bcl10 and Malt1 are essential for FcεRI-induced NF-κB activation and pro-inflammatory cytokine production in mast cells but are dispensable for degranulation and leukotriene secretion, demonstrating that Bcl10/Malt1 selectively uncouple NF-κB-dependent cytokine production from other mast cell responses. Knockout mouse model (Bcl10-/- and Malt1-/-), mast cell activation assays, NF-κB assay The Journal of experimental medicine High 16432253
2006 Bcl10 and Malt1 are required for lysophosphatidic acid (LPA)-induced NF-κB activation in non-immune cells (MEFs); Bcl10 cooperates with PKC for LPA-induced NF-κB but is dispensable for JNK, p38, ERK, and Akt activation, establishing a GPCR-triggered NF-κB pathway through Bcl10/Malt1. Knockout MEFs, NF-κB activation assays, cytokine measurement Proceedings of the National Academy of Sciences of the United States of America High 17095601
2006 Bcl10 is required for NF-κB activation induced by G protein-coupled receptors (GPCRs) in non-lymphoid cells; Bcl10 deficiency blocks NF-κB activation by constitutively active Gα or stimulation with LPA or endothelin-1, but not by TNF-α, LPS, or integrin stimulation. Bcl10-/- cells, constitutively active G protein constructs, specific NF-κB activation assays Proceedings of the National Academy of Sciences of the United States of America High 17179215
2006 CaMKII phosphorylates Bcl10 on Ser138; S138A mutation prolongs Bcl10-induced NF-κB activation, indicating phosphorylation at this site attenuates NF-κB activation as a negative regulatory mechanism. In vitro kinase assay, CaMKII inhibitor (KN93), CaMKII siRNA, S138A mutagenesis, NF-κB reporter assay Molecular immunology High 17052756
2007 Bcl10 is rapidly phosphorylated upon T cell activation; Ser138 is a key phosphorylation residue; a S138A phosphorylation-deficient mutant specifically inhibits TCR-induced actin polymerization without affecting NF-κB activation; Bcl10 silencing (but not Carma1 silencing) impairs TCR-induced F-actin formation, cell spreading, and conjugate formation, and also FcγR-induced actin polymerization and phagocytosis in monocytes. siRNA knockdown, phospho-site mutagenesis, F-actin imaging, phagocytosis assay Journal of immunology High 17371994
2007 Phosphorylation of Bcl10 at S138 promotes ubiquitination and subsequent degradation of Bcl10, downregulating Bcl10 protein levels and negatively regulating TCR-mediated NF-κB activation; S138A mutant shows impaired ubiquitination, reduced degradation, and prolonged NF-κB activation with enhanced IL-2 production. TCR stimulation of T cells, phospho-site mutation (S138A), ubiquitination assay, NF-κB reporter, IL-2 ELISA Molecular and cellular biology High 17502353
2007 PKCβ phosphorylates CARMA1 on Ser668, which is essential for BCR-mediated CARMA1-Bcl10-MALT1 association and IKK activation; downstream IKKβ further facilitates CBM complex formation through positive feedback phosphorylation of CARMA1. Phosphorylation site mutagenesis, co-immunoprecipitation, IKK activation assay in B cells The Journal of experimental medicine High 18086859
2008 Bcl10 undergoes K63-linked polyubiquitination at K31 and K63 in response to T cell activation; ubiquitinated Bcl10 binds NEMO via NEMO's ubiquitin-binding activity; mutation of K31/K63 prevents ubiquitination, NEMO binding, and NF-κB activation without affecting CBM complex assembly. Ubiquitination mapping, site-directed mutagenesis (K31R/K63R), NEMO binding assay, NF-κB activation assay Proceedings of the National Academy of Sciences of the United States of America High 18287044
2008 BCL10 mediates TLR4/LPS-induced NF-κB activation in intestinal epithelial cells through a MyD88-dependent pathway; TLR4 blocking antibody or siRNA reduces BCL10 and IL-8 induction, and Bcl10 is recruited to TLR4 signaling complexes. TLR4 blocking antibody, TLR4 siRNA, dominant-negative MyD88, fluorescence-tagged carrageenan binding, Bcl10 siRNA The Journal of biological chemistry Medium 18252714
2008 The CARMA3-Bcl10-MALT1 (CBM) complex mediates CXCL8/IL-8-induced NF-κB activation and VEGF upregulation in endothelial cells downstream of CXCR2; knockdown of Carma3, Bcl10, or MALT1 inhibits this pathway. siRNA knockdown of CBM components, NF-κB reporter, VEGF ELISA The Journal of biological chemistry Medium 19112107
2008 Multiple protein domains mediate Bcl10-MALT1 interaction: residues Asp80 and Glu84 of helix 5 of the Bcl10 CARD directly contact MALT1; the MALT1 death domain also contributes to the interaction; the 13-aa region downstream of the Bcl10 CARD interacts with MALT1 Ig-like domains. Co-immunoprecipitation, FRET in T cells, molecular modeling, point mutagenesis The Journal of biological chemistry High 18806265
2004 BCL10 mediates LPS/TLR4-induced NF-κB activation via interaction with Pellino2; IRAK-1 acts as the upstream adaptor recruiting BCL10 to the TLR4 complex; BCL10-MALT1-TRAF6-TAK1 cascade transduces the signal; BCL10 oligomerization is required for this function; SOCS3 negatively regulates BCL10 in this pathway. Co-immunoprecipitation, BCL10-deficient macrophage line, NF-κB assay, SOCS3 overexpression The Journal of biological chemistry Medium 15213237 16831874
2005 MALT1 contains nuclear export signals (NES) and regulates cytoplasmic localization of BCL10; MALT1 is involved in nuclear export of BCL10 in an NES-dependent manner, as demonstrated by leptomycin B treatment; this explains nuclear BCL10 in t(1;14) and t(11;18) MALT lymphomas. NES deletion mutants, leptomycin B treatment, subcellular fractionation/immunofluorescence Blood High 16123224
2011 The calcium-dependent phosphatase calcineurin positively regulates CBM complex formation by dephosphorylating Bcl10; calcineurin interacts with the CBM complex; inhibition by cyclosporin A or FK506 or calcineurin siRNA impairs CBM assembly and TCR-induced NF-κB activation, correlating with Bcl10 hyperphosphorylation. Co-immunoprecipitation, in vivo and in vitro phosphatase assay, cyclosporin A/FK506, calcineurin siRNA, NF-κB reporter The Journal of biological chemistry High 21199863
2011 MIB2 E3 ubiquitin ligase is a novel component of the activated BCL10 complex; MIB2 directly interacts with BCL10, promotes autoubiquitination and ubiquitination of IKKγ/NEMO, and recruits/activates TAK1; MIB2 knockdown inhibits BCL10-dependent NF-κB activation. Proteomic pulldown, in vitro translation/pulldown, overexpression, siRNA knockdown, NF-κB reporter The Journal of biological chemistry Medium 21896478
2012 Bcl10 regulates actin dynamics and membrane remodeling downstream of FcγR in macrophages in an NF-κB-independent manner; Bcl10 depletion impairs Rac1 and PI3K activation, leads to abortive phagocytic cup with excess PI(4,5)P2, Cdc42, and F-actin; Bcl10 forms a complex with clathrin adaptors AP1 and EpsinR and is required to deliver OCRL phosphatase locally. siRNA depletion, live-cell imaging, phagocytosis assay, Co-IP, PI analysis Developmental cell High 23153494
2013 The reconstituted CBM signalosome is a helical filamentous assembly; substoichiometric CARMA1 nucleates Bcl10 CARD filament formation in a highly cooperative process; the Bcl10 CARD filament structure was determined by crystallography, NMR, and EM; structure-guided mutagenesis confirmed interfaces for Bcl10 filament assembly and MALT1 activation. Reconstitution, cryo-EM, crystallography, NMR, electron microscopy, site-directed mutagenesis, NF-κB reporter assay Molecular cell High 24074955
2013 USP9X deubiquitinating enzyme interacts with Bcl10 and removes TCR-induced ubiquitin chains from Bcl10, facilitating association of CARMA1 with the Bcl10-Malt1 sub-complex; USP9X knockdown attenuates NF-κB activation and T cell proliferation. Co-immunoprecipitation, USP9X knockdown, NF-κB activation assay, T cell proliferation assay Proceedings of the National Academy of Sciences of the United States of America Medium 23690623
2014 TCR signals to NF-κB are transmitted via a cytosolic p62-Bcl10-Malt1-IKK signalosome; p62 is required for Bcl10-Malt1 clustering; IKK is recruited to and activated within this signalosome; TAK1 and IKK activities are required for IKK phosphorylation but not signalosome assembly, ordering the pathway. Biochemical fractionation, confocal imaging, p62-/- T cells, kinase inhibitors, Co-IP Science signaling High 24825920
2015 Constitutively active CARD11 L225LI associates with BCL10 and MALT1 to simultaneously activate NF-κB and JNK; genetic deficiency of BCL10 or MALT1 completely rescues lymphoproliferation in CARD11 gain-of-function mice, demonstrating BCL10 is essential downstream of oncogenic CARD11 for both NF-κB and JNK activation. Conditional knock-in mouse, BCL10/MALT1 knockout rescue epistasis, JNK inhibitor Proceedings of the National Academy of Sciences of the United States of America High 26668357
2016 CARD14 psoriasis mutants (E138A, G117S) constitutively interact with BCL10 and MALT1 and trigger BCL10- and MALT1-dependent NF-κB activation in keratinocytes by disrupting the autoinhibitory effect of the CARD14 linker region on BCL10 binding; CARD14 E138A also stimulates MALT1 paracaspase activity. Co-immunoprecipitation, NF-κB reporter, MALT1 paracaspase activity assay, siRNA knockdown The Biochemical journal High 27071417
2018 Cryo-EM structure of the BCL10 CARD filament at 4.0 Å reveals the CARD-CARD interaction interfaces; CARMA1 serves as a hub for star-shaped filamentous BCL10 networks and decreases BCL10 polymerization lag; MALT1 cooperatively binds BCL10 filaments and immediately dimerizes; TRAF6 cooperatively decorates CBM filaments to form higher-order assemblies. Cryo-EM structure determination, time-lapse confocal imaging, in vitro polymerization assay, EM Proceedings of the National Academy of Sciences of the United States of America High 29382759
2018 GSK3β phosphorylates BCL10 and is required for CBM complex formation; pharmacological inhibition or RNAi knockdown of GSK3β reduces BCL10 phosphorylation, CBM complex formation, MALT1-catalyzed cleavage of BCL10/RelB/CYLD, IκBα degradation, and NF-κB activation in activated T cells. GSK3β inhibitors, siRNA, phosphorylation assay, Co-IP, NF-κB reporter, MALT1 cleavage assay Scientific reports Medium 29358699
2011 CaMKII is recruited to the immunological synapse where it interacts with and phosphorylates the Bcl10 CARD domain; this phosphorylation regulates interactions within the Carma1-Bcl10-Malt1 complex and the TCR-induced ubiquitinations of Bcl10 and IKKγ. Immunological synapse imaging, co-immunoprecipitation, in vitro kinase assay, ubiquitination assay Molecular immunology High 21513986
2001 Bcl10 interacts with TRAF2 and cIAPs; phosphorylation of Bcl10 regulates these interactions (phospho-Bcl10 binds cIAPs and dissociates from TRAF2); hyperphosphorylation of Bcl10 promotes apoptosis; the cIAP-binding site on Bcl10 is required for apoptosis induction. Co-immunoprecipitation, Bcl10 transgenic mice, mutagenesis, apoptosis assay Oncogene Medium 11466612
2010 The CARMA3-Bcl10-MALT1 signalosome links thrombin/PAR-1 (GPCR) signaling to IKK/NF-κB activation in endothelial cells; this signalosome requires β-arrestin 2 (not PDK1) for assembly, distinguishing it from the lymphocyte CARMA1 complex; Bcl10-Malt1 signaling is required for thrombin-induced monocyte-endothelial adhesion. siRNA knockdown, Co-IP, NF-κB reporter, monocyte-endothelial adhesion assay The Journal of biological chemistry Medium 21041303
2010 Bcl10 links palmitate/saturated fatty acid signaling to NF-κB activation in hepatocytes via diacylglycerol-PKC axis; Bcl10-/- mice are protected from hepatic NF-κB activation and insulin resistance after high-fat diet; MALT1 is dispensable in this context, revealing a non-classical Bcl10 role. Bcl10-/- and Malt1-/- mouse models, high-fat diet experiment, NF-κB assay, insulin resistance measurement Cell reports High 22708078
2021 TRIM41 E3 ubiquitin ligase directly interacts with BCL10 and catalyzes K63-linked polyubiquitination of BCL10; this ubiquitination recruits NEMO and activates NF-κB and TBK1-IRF3 pathways during innate antiviral responses; TRIM41 deficiency impairs innate cytokine and interferon production. Co-IP, in vitro/in vivo ubiquitination assay, TRIM41-/- macrophages, viral infection models Signal transduction and targeted therapy High 33640899
2021 USP12 deubiquitinase stabilizes BCL10 by removing ubiquitin chains, thereby promoting NF-κB signaling in CD4+ T cells; this regulatory mechanism is specific to CD4+ (not CD8+) T cells. Co-immunoprecipitation, deubiquitination assay, USP12-/- mice, T cell activation/differentiation assays Cell death and differentiation Medium 33941870
2000 BCL10 nuclear localization is specifically altered in MALT lymphomas; in normal B cells BCL10 is predominantly cytoplasmic, while in MALT lymphomas with t(1;14)(p22;q32) BCL10 is strongly expressed in both nucleus and cytoplasm, establishing subcellular mislocalization as a disease-associated mechanism. Immunohistochemistry on formalin-fixed paraffin-embedded tissues, monoclonal antibodies The American journal of pathology Medium 11021819
2009 BCL10 is required for carrageenan-induced NF-κB activation and IL-8 production in human intestinal epithelial cells via the TLR4/MyD88/IRAK pathway; siRNA knockdown of BCL10 markedly reduces carrageenan-induced IL-8 and NF-κB activation. siRNA knockdown, NF-κB reporter, IL-8 ELISA, BCL10 western blot American journal of physiology. Gastrointestinal and liver physiology Medium 17095757
2019 Bcl10 is required for the development and suppressive function of Foxp3+ regulatory T cells; T cell-specific or Treg-specific Bcl10 deletion impairs Treg development and function, leading to lethal autoimmunity; Bcl10-deficient Tregs lose effector/suppressive gene expression and convert to IFNγ-producing proinflammatory cells. Conditional knockout (Bcl10fl/fl Foxp3cre), adoptive transfer, gene expression profiling Cellular & molecular immunology High 31595055

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. Cell 534 9989495
2001 Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure. Cell 438 11163238
2003 Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO. Nature 435 14695475
2001 Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway. The Journal of biological chemistry 349 11262391
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 334 19112107
1999 Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). Nature genetics 311 10319863
2015 CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis. Journal of molecular and cellular cardiology 223 26423156
2010 Antigen receptor signaling to NF-kappaB via CARMA1, BCL10, and MALT1. Cold Spring Harbor perspectives in biology 193 20685844
2001 T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10. Blood 180 11493468
2020 Camrelizumab Plus Apatinib in Patients With Advanced Cervical Cancer (CLAP): A Multicenter, Open-Label, Single-Arm, Phase II Trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 169 33052760
2001 Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappaB activation. FEBS letters 167 11356195
2003 Defective development and function of Bcl10-deficient follicular, marginal zone and B1 B cells. Nature immunology 151 12910267
2000 BCL10 expression in normal and neoplastic lymphoid tissue. Nuclear localization in MALT lymphoma. The American journal of pathology 150 11021819
2013 Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-induced filamentous assembly. Molecular cell 149 24074955
2008 Toll-like receptor 4 mediates induction of the Bcl10-NFkappaB-interleukin-8 inflammatory pathway by carrageenan in human intestinal epithelial cells. The Journal of biological chemistry 138 18252714
1999 CIPER, a novel NF kappaB-activating protein containing a caspase recruitment domain with homology to Herpesvirus-2 protein E10. The Journal of biological chemistry 132 10187770
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
2013 In planta expression or delivery of potato aphid Macrosiphum euphorbiae effectors Me10 and Me23 enhances aphid fecundity. Molecular plant-microbe interactions : MPMI 120 23194342
2008 NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation. Proceedings of the National Academy of Sciences of the United States of America 120 18287044
2004 Degradation of Bcl10 induced by T-cell activation negatively regulates NF-kappa B signaling. Molecular and cellular biology 119 15082780
2006 Carrageenan induces interleukin-8 production through distinct Bcl10 pathway in normal human colonic epithelial cells. American journal of physiology. Gastrointestinal and liver physiology 118 17095757
2014 The CARD11-BCL10-MALT1 (CBM) signalosome complex: Stepping into the limelight of human primary immunodeficiency. The Journal of allergy and clinical immunology 115 25087226
2006 Essential role for IkappaB kinase beta in remodeling Carma1-Bcl10-Malt1 complexes upon T cell activation. Molecular cell 110 16818229
2006 The Bcl10-Malt1 complex segregates Fc epsilon RI-mediated nuclear factor kappa B activation and cytokine production from mast cell degranulation. The Journal of experimental medicine 106 16432253
2005 MALT lymphoma with t(14;18)(q32;q21)/IGH-MALT1 is characterized by strong cytoplasmic MALT1 and BCL10 expression. The Journal of pathology 106 15682443
1999 mE10, a novel caspase recruitment domain-containing proapoptotic molecule. The Journal of biological chemistry 102 10187815
2007 IkappaB kinase beta-induced phosphorylation of CARMA1 contributes to CARMA1 Bcl10 MALT1 complex formation in B cells. The Journal of experimental medicine 92 18086859
2004 The roles of CARMA1, Bcl10, and MALT1 in antigen receptor signaling. Seminars in immunology 92 15541657
2008 Multiple ITAM-coupled NK-cell receptors engage the Bcl10/Malt1 complex via Carma1 for NF-kappaB and MAPK activation to selectively control cytokine production. Blood 91 18192506
2006 cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas. The Journal of clinical investigation 89 16395405
2018 Assembly mechanism of the CARMA1-BCL10-MALT1-TRAF6 signalosome. Proceedings of the National Academy of Sciences of the United States of America 86 29382759
2018 The CBM-opathies-A Rapidly Expanding Spectrum of Human Inborn Errors of Immunity Caused by Mutations in the CARD11-BCL10-MALT1 Complex. Frontiers in immunology 85 30283440
2011 The Ca2+-dependent phosphatase calcineurin controls the formation of the Carma1-Bcl10-Malt1 complex during T cell receptor-induced NF-kappaB activation. The Journal of biological chemistry 85 21199863
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
2000 BCL10 gene mutation in lymphoma. Blood 85 10845924
2006 Bcl10 and Malt1 control lysophosphatidic acid-induced NF-kappaB activation and cytokine production. Proceedings of the National Academy of Sciences of the United States of America 83 17095601
2006 The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-kappaB from Toll-like receptor 4. The Journal of biological chemistry 82 16831874
2014 Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity. The Journal of clinical investigation 79 25365219
2008 Carrageenan-induced NFkappaB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10. Biochimica et biophysica acta 79 18452717
2006 Bcl10 plays a critical role in NF-kappaB activation induced by G protein-coupled receptors. Proceedings of the National Academy of Sciences of the United States of America 79 17179215
2017 The CARMA3-Bcl10-MALT1 Signalosome Drives NFκB Activation and Promotes Aggressiveness in Angiotensin II Receptor-Positive Breast Cancer. Cancer research 74 29259013
2015 Lymphomagenic CARD11/BCL10/MALT1 signaling drives malignant B-cell proliferation via cooperative NF-κB and JNK activation. Proceedings of the National Academy of Sciences of the United States of America 72 26668357
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
2016 Role of the CARMA1/BCL10/MALT1 complex in lymphoid malignancies. Current opinion in hematology 66 27135977
2012 The NF-κB signaling protein Bcl10 regulates actin dynamics by controlling AP1 and OCRL-bearing vesicles. Developmental cell 66 23153494
2010 The CARMA3-Bcl10-MALT1 signalosome promotes angiotensin II-dependent vascular inflammation and atherogenesis. The Journal of biological chemistry 66 20605784
2016 Lymphocyte signaling and activation by the CARMA1-BCL10-MALT1 signalosome. Biological chemistry 64 27420898
2000 Regulatory mechanisms of TRAF2-mediated signal transduction by Bcl10, a MALT lymphoma-associated protein. The Journal of biological chemistry 61 10753917
2016 Psoriasis mutations disrupt CARD14 autoinhibition promoting BCL10-MALT1-dependent NF-κB activation. The Biochemical journal 55 27071417
2013 Regulation of T cell function by the ubiquitin-specific protease USP9X via modulating the Carma1-Bcl10-Malt1 complex. Proceedings of the National Academy of Sciences of the United States of America 53 23690623
2004 Nuclear expression of BCL10 or nuclear factor kappa B predicts Helicobacter pylori-independent status of early-stage, high-grade gastric mucosa-associated lymphoid tissue lymphomas. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 51 15337797
2012 Prolongation of carrageenan-induced inflammation in human colonic epithelial cells by activation of an NFκB-BCL10 loop. Biochimica et biophysica acta 50 22579587
2013 BCL10 as a useful marker for pancreatic acinar cell carcinoma, especially using endoscopic ultrasound cytology specimens. Pathology international 46 23530562
2007 Bcl10 controls TCR- and FcgammaR-induced actin polymerization. Journal of immunology (Baltimore, Md. : 1950) 46 17371994
2018 Aphid effector Me10 interacts with tomato TFT7, a 14-3-3 isoform involved in aphid resistance. The New phytologist 45 30357852
2017 Zinc rescues obesity-induced cardiac hypertrophy via stimulating metallothionein to suppress oxidative stress-activated BCL10/CARD9/p38 MAPK pathway. Journal of cellular and molecular medicine 45 28158919
2014 Folic acid conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel for site specific delivery of hydrophobic drugs to cancer cells. Journal of nanobiotechnology 45 25026938
2009 Emu-BCL10 mice exhibit constitutive activation of both canonical and noncanonical NF-kappaB pathways generating marginal zone (MZ) B-cell expansion as a precursor to splenic MZ lymphoma. Blood 45 19696203
2018 BCL10 - Bridging CARDs to Immune Activation. Frontiers in immunology 44 30022982
2013 Carrageenan-induced colonic inflammation is reduced in Bcl10 null mice and increased in IL-10-deficient mice. Mediators of inflammation 44 23766559
2004 BCL10 mediates lipopolysaccharide/toll-like receptor-4 signaling through interaction with Pellino2. The Journal of biological chemistry 43 15213237
2012 Bcl10 links saturated fat overnutrition with hepatocellular NF-kB activation and insulin resistance. Cell reports 42 22708078
2010 Platelet-activating factor-induced NF-kappaB activation and IL-8 production in intestinal epithelial cells are Bcl10-dependent. Inflammatory bowel diseases 42 19714753
2007 Bcl10 mediates LPS-induced activation of NF-kappaB and IL-8 in human intestinal epithelial cells. American journal of physiology. Gastrointestinal and liver physiology 42 17540779
2011 The E3 ubiquitin ligase mind bomb-2 (MIB2) protein controls B-cell CLL/lymphoma 10 (BCL10)-dependent NF-κB activation. The Journal of biological chemistry 41 21896478
2021 Genomic profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: a secondary analysis of the CLAP trial. Journal for immunotherapy of cancer 40 34011535
2007 Post-translational modifications regulate distinct functions of CARMA1 and BCL10. Trends in immunology 40 17468049
2001 The Carvedilol and ACE-Inhibitor Remodelling Mild Heart Failure EvaluatioN trial (CARMEN)--rationale and design. Cardiovascular drugs and therapy 39 11504166
2010 Lipopolysaccharide-induced activation of NF-κB non-canonical pathway requires BCL10 serine 138 and NIK phosphorylations. Experimental cell research 37 20466000
2014 T cell receptor signals to NF-κB are transmitted by a cytosolic p62-Bcl10-Malt1-IKK signalosome. Science signaling 36 24825920
2006 Bcl10 is phosphorylated on Ser138 by Ca2+/calmodulin-dependent protein kinase II. Molecular immunology 36 17052756
2008 A20 is a negative regulator of BCL10- and CARMA3-mediated activation of NF-kappaB. Journal of cell science 35 18349075
2007 Bcl10 plays a divergent role in NK cell-mediated cytotoxicity and cytokine generation. Journal of immunology (Baltimore, Md. : 1950) 35 17785812
2008 Multiple protein domains mediate interaction between Bcl10 and MALT1. The Journal of biological chemistry 34 18806265
2007 Phosphorylation of Bcl10 negatively regulates T-cell receptor-mediated NF-kappaB activation. Molecular and cellular biology 34 17502353
2005 MALT1 contains nuclear export signals and regulates cytoplasmic localization of BCL10. Blood 34 16123224
2018 Ubiquitination and phosphorylation of the CARD11-BCL10-MALT1 signalosome in T cells. Cellular immunology 33 30514565
2009 STAT5 regulation of BCL10 parallels constitutive NFkappaB activation in lymphoid tumor cells. Molecular cancer 32 19709433
2007 Transcriptional profiling of the nuclear factor-kappaB pathway identifies a subgroup of primary lymphoma of the central nervous system with low BCL10 expression. Journal of neuropathology and experimental neurology 32 17356384
1999 Bcl10 is not a target for frequent mutation in human carcinomas. British journal of cancer 30 10408401
2009 COP9 signalosome controls the Carma1-Bcl10-Malt1 complex upon T-cell stimulation. EMBO reports 29 19444310
2008 Lipopolysaccharide activates NF-kappaB by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells. American journal of physiology. Gastrointestinal and liver physiology 29 18718996
2018 GSK3β modulates NF-κB activation and RelB degradation through site-specific phosphorylation of BCL10. Scientific reports 28 29358699
2006 Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 27 16648871
2011 CaMKII targets Bcl10 in T-cell receptor induced activation of NF-κB. Molecular immunology 26 21513986
2018 Ancient Origin of the CARD-Coiled Coil/Bcl10/MALT1-Like Paracaspase Signaling Complex Indicates Unknown Critical Functions. Frontiers in immunology 25 29881386
1999 Mutations in Bcl10 are very rare in colorectal cancer. British journal of cancer 24 10408399
2007 Bcl10/Malt1 signaling is essential for TCR-induced NF-kappaB activation in thymocytes but dispensable for positive or negative selection. Journal of immunology (Baltimore, Md. : 1950) 23 17202357
2021 TRIM41 is required to innate antiviral response by polyubiquitinating BCL10 and recruiting NEMO. Signal transduction and targeted therapy 22 33640899
2014 Bcl10 mediates angiotensin II-induced cardiac damage and electrical remodeling. Hypertension (Dallas, Tex. : 1979) 22 25185127
2003 Infrequent somatic Fas mutations but no evidence of Bcl10 mutations or t(11;18) in primary cutaneous MALT-type lymphoma. The Journal of pathology 22 12950026
2008 BCL10 nuclear expression and t(11;18)(q21;q21) indicate nonresponsiveness to Helicobacter pylori eradication of Chinese primary gastric MALT lymphoma. International journal of hematology 21 18949449
2001 Interchangeable binding of Bcl10 to TRAF2 and cIAPs regulates apoptosis signaling. Oncogene 21 11466612
2019 Bcl10 is required for the development and suppressive function of Foxp3+ regulatory T cells. Cellular & molecular immunology 20 31595055
2010 Interleukin-2 induces NF-kappaB activation through BCL10 and affects its subcellular localization in natural killer lymphoma cells. The Journal of pathology 20 20235165
2021 USP12 promotes CD4+ T cell responses through deubiquitinating and stabilizing BCL10. Cell death and differentiation 19 33941870
2014 AIP augments CARMA1-BCL10-MALT1 complex formation to facilitate NF-κB signaling upon T cell activation. Cell communication and signaling : CCS 19 25245034
2022 The combination of gemcitabine and ginsenoside Rh2 enhances the immune function of dendritic cells against pancreatic cancer via the CARD9-BCL10-MALT1 / NF-κB pathway. Clinical immunology (Orlando, Fla.) 18 36581220
2006 CIAP2 inhibits anigen receptor signaling by targeting Bcl10 for degredation. Cell cycle (Georgetown, Tex.) 18 16775419
1999 Infrequent BCL10 mutations in B-cell non-Hodgkin's lymphomas. Japanese journal of cancer research : Gann 18 10665648