Gene Symbol: CARMA1
Description: caspase recruitment domain family member 11
Alias: BENTA, BIMP3, CARMA1, IMD11, IMD11A, PPBL, caspase recruitment domain-containing protein 11, CARD-containing MAGUK protein 1, bcl10-interacting maguk protein 3, carma 1
Species: human
Products:     CARMA1

Top Publications

  1. Wang D, Matsumoto R, You Y, Che T, Lin X, Gaffen S, et al. CD3/CD28 costimulation-induced NF-kappaB activation is mediated by recruitment of protein kinase C-theta, Bcl10, and IkappaB kinase beta to the immunological synapse through CARMA1. Mol Cell Biol. 2004;24:164-71 pubmed
    b>CARMA1 (also known as CARD11) is a scaffold molecule and contains a caspase-recruitment domain (CARD) and a membrane-associated guanylate kinase-like (MAGUK) domain...
  2. Lin X, Wang D. The roles of CARMA1, Bcl10, and MALT1 in antigen receptor signaling. Semin Immunol. 2004;16:429-35 pubmed
    ..Recent studies demonstrate that CARMA1, a scaffold protein, plays an essential role in mediating TCR- or BCR-induced NF-kappaB activation by recruiting ..
  3. Snow A, Xiao W, Stinson J, Lu W, Chaigne Delalande B, Zheng L, et al. Congenital B cell lymphocytosis explained by novel germline CARD11 mutations. J Exp Med. 2012;209:2247-61 pubmed publisher
  4. Bertin J, Wang L, Guo Y, Jacobson M, Poyet J, Srinivasula S, et al. CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B. J Biol Chem. 2001;276:11877-82 pubmed
    ..These findings suggest that CARD11 and CARD14 are novel MAGUK family members that function as upstream activators of BCL10 and NF-kappaB signaling. ..
  5. Shinohara H, Yasuda T, Aiba Y, Sanjo H, Hamadate M, Watarai H, et al. PKC beta regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1. J Exp Med. 2005;202:1423-31 pubmed
    ..TAK1 interacts with the phosphorylated CARMA1 (also known as caspase recruitment domain [CARD]11, Bimp3) and this interaction is mediated by PKCbeta...
  6. Lamason R, McCully R, Lew S, Pomerantz J. Oncogenic CARD11 mutations induce hyperactive signaling by disrupting autoinhibition by the PKC-responsive inhibitory domain. Biochemistry. 2010;49:8240-50 pubmed publisher
    ..Our results establish a mechanism that explains how DLBCL-associated mutations in CARD11 can initiate spontaneous, receptor-independent activation of NF-?B. ..
  7. Thome M. CARMA1, BCL-10 and MALT1 in lymphocyte development and activation. Nat Rev Immunol. 2004;4:348-59 pubmed
  8. Thome M, Weil R. Post-translational modifications regulate distinct functions of CARMA1 and BCL10. Trends Immunol. 2007;28:281-8 pubmed
    ..Phosphorylation of the CARMA1 and BCL10 proteins and ubiquitylation of BCL10 affect the formation and stability of the CARMA1-BCL10-MALT1 (CBM) ..
  9. Bidère N, Ngo V, Lee J, Collins C, Zheng L, Wan F, et al. Casein kinase 1alpha governs antigen-receptor-induced NF-kappaB activation and human lymphoma cell survival. Nature. 2009;458:92-6 pubmed publisher
    ..Antigen receptor stimulation assembles an NF-kappaB activating platform containing the scaffold protein CARMA1 (also called CARD11), the adaptor BCL10 and the paracaspase MALT1 (the CBM complex), linked to the inhibitor of NF-..

More Information

Publications121 found, 100 shown here

  1. Blonska M, Joo D, Zweidler McKay P, Zhao Q, Lin X. CARMA1 controls Th2 cell-specific cytokine expression through regulating JunB and GATA3 transcription factors. J Immunol. 2012;188:3160-8 pubmed publisher
    The scaffold protein CARMA1 is required for the TCR-induced lymphocyte activation. In this study, we show that CARMA1 also plays an essential role in T cell differentiation...
  2. Sun L, Deng L, Ea C, Xia Z, Chen Z. The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol Cell. 2004;14:289-301 pubmed
    ..These results reveal an oligomerization --> ubiquitination --> phosphorylation cascade that culminates in NF-kappaB activation in T lymphocytes. ..
  3. Matsumoto R, Wang D, Blonska M, Li H, Kobayashi M, Pappu B, et al. Phosphorylation of CARMA1 plays a critical role in T Cell receptor-mediated NF-kappaB activation. Immunity. 2005;23:575-85 pubmed
    b>CARMA1 mediates T cell receptor (TCR)-induced NF-kappaB activation. However, how TCR links to CARMA1 in the signaling pathway is not clear. Here, we show that CARMA1 is inducibly phosphorylated after TCR-CD28 costimulation...
  4. Stilo R, Liguoro D, Di Jeso B, Formisano S, Consiglio E, Leonardi A, et al. Physical and functional interaction of CARMA1 and CARMA3 with Ikappa kinase gamma-NFkappaB essential modulator. J Biol Chem. 2004;279:34323-31 pubmed
    ..b>CARMA1 plays a critical role in mediating activation of the NFkappaB transcription factor following antigen receptor ..
  5. Moreno Garcia M, Sommer K, Shinohara H, Bandaranayake A, Kurosaki T, Rawlings D. MAGUK-controlled ubiquitination of CARMA1 modulates lymphocyte NF-kappaB activity. Mol Cell Biol. 2010;30:922-34 pubmed publisher
    The adaptor protein CARMA1 is required for antigen receptor-triggered activation of IKK and JNK in lymphocytes. Once activated, the events that subsequently turn off the CARMA1 signalosome are unknown...
  6. Wang D, You Y, Case S, McAllister Lucas L, Wang L, DiStefano P, et al. A requirement for CARMA1 in TCR-induced NF-kappa B activation. Nat Immunol. 2002;3:830-5 pubmed
    ..Using a somatic mutagenesis approach, we cloned a CARMA1-deficient T cell line...
  7. Sommer K, Guo B, Pomerantz J, Bandaranayake A, Moreno Garcia M, Ovechkina Y, et al. Phosphorylation of the CARMA1 linker controls NF-kappaB activation. Immunity. 2005;23:561-74 pubmed
    PKC isoforms and CARMA1 play crucial roles in immunoreceptor-dependent NF-kappaB activation. We tested whether PKC-dependent phosphorylation of CARMA1 directly regulates this signaling cascade...
  8. Ishiguro K, Green T, Rapley J, Wachtel H, Giallourakis C, Landry A, et al. Ca2+/calmodulin-dependent protein kinase II is a modulator of CARMA1-mediated NF-kappaB activation. Mol Cell Biol. 2006;26:5497-508 pubmed
    b>CARMA1 is a central regulator of NF-kappaB activation in lymphocytes. CARMA1 and Bcl10 functionally interact and control NF-kappaB signaling downstream of the T-cell receptor (TCR)...
  9. Shambharkar P, Blonska M, Pappu B, Li H, You Y, Sakurai H, et al. Phosphorylation and ubiquitination of the IkappaB kinase complex by two distinct signaling pathways. EMBO J. 2007;26:1794-805 pubmed
    ..Here, we demonstrate that CARMA1, a key scaffold molecule, is essential to regulate NEMO ubiquitination upon T-cell receptor (TCR) stimulation...
  10. Lee K, D Acquisto F, Hayden M, Shim J, Ghosh S. PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation. Science. 2005;308:114-8 pubmed
    ..Hence, PDK1 plays a critical role by nucleating the TCR-induced NF-kappaB activation pathway in T cells. ..
  11. Lenz G, Davis R, Ngo V, Lam L, George T, Wright G, et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science. 2008;319:1676-9 pubmed publisher
    ..These results demonstrate that CARD11 is a bona fide oncogenein DLBCL, providing a genetic rationale for the development of pharmacological inhibitors of the CARD11 pathway for DLBCL therapy. ..
  12. Dong G, Chanudet E, Zeng N, Appert A, Chen Y, Au W, et al. A20, ABIN-1/2, and CARD11 mutations and their prognostic value in gastrointestinal diffuse large B-cell lymphoma. Clin Cancer Res. 2011;17:1440-51 pubmed publisher
    ..We show further evidence of NF-?B pathway genetic abnormalities in DLBCL, which are potentially valuable in the prognosis and design of future therapeutic strategies. ..
  13. Pomerantz J, Denny E, Baltimore D. CARD11 mediates factor-specific activation of NF-kappaB by the T cell receptor complex. EMBO J. 2002;21:5184-94 pubmed
    ..These results implicate CARD11 in factor- specific activation of NF-kappaB by the TCR complex and establish a role for a MAGUK family member in antigen receptor signaling. ..
  14. Oeckinghaus A, Wegener E, Welteke V, Ferch U, Arslan S, Ruland J, et al. Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation. EMBO J. 2007;26:4634-45 pubmed
    ..T-cell receptor (TCR) engagement induces the formation of the Carma1-Bcl10-Malt1 (CBM) complex that is essential for activation of the IkappaB kinase (IKK)/NF-kappaB pathway...
  15. McCully R, Pomerantz J. The protein kinase C-responsive inhibitory domain of CARD11 functions in NF-kappaB activation to regulate the association of multiple signaling cofactors that differentially depend on Bcl10 and MALT1 for association. Mol Cell Biol. 2008;28:5668-86 pubmed publisher
    ..Using Bcl10- and MALT1-deficient cells, we show that CARD11 can recruit signaling cofactors independently of one another in a signal-inducible manner. ..
  16. Montesinos Rongen M, Schmitz R, Brunn A, Gesk S, Richter J, Hong K, et al. Mutations of CARD11 but not TNFAIP3 may activate the NF-kappaB pathway in primary CNS lymphoma. Acta Neuropathol. 2010;120:529-35 pubmed publisher
  17. Gaide O, Favier B, Legler D, Bonnet D, Brissoni B, Valitutti S, et al. CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation. Nat Immunol. 2002;3:836-43 pubmed
    b>CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane...
  18. Li X, Cai Y. Methylation-Based Classification of Cervical Squamous Cell Carcinoma into Two New Subclasses Differing in Immune-Related Gene Expression. Int J Mol Sci. 2018;19: pubmed publisher
    ..Our analyses provide a classification of the largest CSCC subtype into two new subclasses, revealing they harbored differences in immune-related gene expression. ..
  19. Boi M, Gaudio E, Bonetti P, Kwee I, Bernasconi E, Tarantelli C, et al. The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs. Clin Cancer Res. 2015;21:1628-38 pubmed publisher
    ..Together with the data coming from the ongoing phase I study, the in vitro and in vivo data presented here provide the basis for further clinical investigation of OTX015 as single agent and in combination therapies. ..
  20. Suddason T, Anwar S, Charlaftis N, Gallagher E. T-Cell-Specific Deletion of Map3k1 Reveals the Critical Role for Mekk1 and Jnks in Cdkn1b-Dependent Proliferative Expansion. Cell Rep. 2016;14:449-457 pubmed publisher
    ..Mekk1 regulates Jnk activation in iNKT cells and binds and transfers Lys63-linked poly-ubiquitin onto Carma1. Map3k1 is critical for the regulation of p27(Kip1) (encoded by Cdkn1b).
  21. Nachbur U, Silke J. Killing Lymphoma with Smac-Mimetics: As Easy as ABC?. Cancer Cell. 2016;29:425-427 pubmed publisher
    ..In this issue of Cancer Cell, Yang and colleagues (2016) identify cIAPs at the CARD11-MALT1-BCL10 complex in the ABC subtype of diffuse large B cell lymphoma (DLBCL), making this malignancy a prime target for these drugs. ..
  22. Bergerson J, Freeman A. An Update on Syndromes with a Hyper-IgE Phenotype. Immunol Allergy Clin North Am. 2019;39:49-61 pubmed publisher
    ..This article focuses on loss of function STAT3 mutations causing autosomal-dominant hyper-IgE syndrome and dedicator of cytokinesis 8 deficiency, with discussion of other more recently described diseases. ..
  23. Yang Y, Shaffer A, Emre N, Ceribelli M, Zhang M, Wright G, et al. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell. 2012;21:723-37 pubmed publisher
    ..Blockade of B cell receptor signaling using the BTK inhibitor ibrutinib also downregulates IRF4 and consequently synergizes with lenalidomide in killing ABC DLBCLs, suggesting attractive therapeutic strategies. ..
  24. D Andrea E, Ferravante A, Scudiero I, Zotti T, Reale C, Pizzulo M, et al. The Dishevelled, EGL-10 and pleckstrin (DEP) domain-containing protein DEPDC7 binds to CARMA2 and CARMA3 proteins, and regulates NF-κB activation. PLoS ONE. 2014;9:e116062 pubmed publisher
    ..activation following G protein-coupled receptors stimulation, or stimuli that require CARMA2 and CARMA3, but not CARMA1. Thus, this study identifies DEPDC7 as a CARMA interacting molecule, and provides evidence that DEPDC7 may be ..
  25. Farmanbar A, Firouzi S, Makałowski W, Kneller R, Iwanaga M, Utsunomiya A, et al. Mutational Intratumor Heterogeneity is a Complex and Early Event in the Development of Adult T-cell Leukemia/Lymphoma. Neoplasia. 2018;20:883-893 pubmed publisher
    ..Our findings suggest that clonal/subclonal architecture might be a useful measure for prognostic purposes and personalized assessment of the therapeutic response. ..
  26. Kahl B. Follicular lymphoma: are we ready for a risk-adapted approach?. Hematology Am Soc Hematol Educ Program. 2017;2017:358-364 pubmed publisher
    ..However, several unmet needs remain, including a better ability to identify high-risk patients at diagnosis, the development of predictive biomarkers for targeted agents, and strategies to reduce the risk of transformation...
  27. Li L, Li Q, Wang Q, Liu L, Li R, Liu H, et al. Rare copy number variants in the genome of Chinese female children and adolescents with Turner syndrome. Biosci Rep. 2019;39: pubmed publisher
    ..Our results indicate that CARD11 gene is one of the mutated genes involved in TS disease. However, this CNV is rare and its contribution to TS phenotype requires further study. ..
  28. Ma Y, Liao Z, Xu Y, Zhong Z, Wang X, Zhang F, et al. Characteristics of CARMA1-BCL10-MALT1-A20-NF-κB expression in T cell-acute lymphocytic leukemia. Eur J Med Res. 2014;19:62 pubmed publisher
    ..of A20 and its regulating factors, including upstream regulators and the CBM complex, which includes CARMA1, BCL10, and MALT1...
  29. Torres J, Martinez Barricarte R, García Gómez S, Mazariegos M, Itan Y, Boisson B, et al. Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity. J Clin Invest. 2014;124:5239-48 pubmed publisher
    ..The results of this study indicate that inherited BCL10 deficiency should be considered in patients with combined immunodeficiency with B cell, T cell, and fibroblast defects. ..
  30. Shi G, Cheng C, Wang T, Li S, Fan Y, Zhu K. Association between atopic dermatitis-related single nucleotide polymorphisms rs4722404 and psoriasis vulgaris in a southern Chinese cohort. Genet Mol Res. 2016;15: pubmed publisher
    ..023 for CC+CT genotype). The results of this study suggested that the SNP rs4722404 in CARD11 could increase the risk of early-onset PsV. Further studies must analyze the potential function of CARD11 in the pathogenesis of PsV. ..
  31. Greenawalt D, Liang W, Saif S, Johnson J, Todorov P, Dulak A, et al. Comparative analysis of primary versus relapse/refractory DLBCL identifies shifts in mutation spectrum. Oncotarget. 2017;8:99237-99244 pubmed publisher
    ..These findings hold significance for a number of emerging targeted therapies aligned to genetic targets and biomarkers in DLBCL, reinforcing the importance of time-of-treatment biomarker screening during DLBCL therapy selection...
  32. Ohnuma K, Uchiyama M, Yamochi T, Nishibashi K, Hosono O, Takahashi N, et al. Caveolin-1 triggers T-cell activation via CD26 in association with CARMA1. J Biol Chem. 2007;282:10117-31 pubmed
    ..We also demonstrated that the cytoplasmic tail of CD26 interacts with CARMA1 in T-cells, resulting in signaling events that lead to NF-kappaB activation...
  33. Tanabe S, Kawabata T, Aoyagi K, Yokozaki H, Sasaki H. Gene expression and pathway analysis of CTNNB1 in cancer and stem cells. World J Stem Cells. 2016;8:384-395 pubmed
    ..The results indicate that the epithelial-mesenchymal transition (EMT)-related gene CTNNB1 plays an important role in the regulation of stem cell pluripotency and cancer signaling. ..
  34. Wang L, Guo Y, Huang W, Ke X, Poyet J, Manji G, et al. Card10 is a novel caspase recruitment domain/membrane-associated guanylate kinase family member that interacts with BCL10 and activates NF-kappa B. J Biol Chem. 2001;276:21405-9 pubmed
    ..We propose that CARD10 functions as a molecular scaffold for the assembly of a BCL10 signaling complex that activates NF-kappaB. ..
  35. Liu Y, Song R, Gao Y, Li Y, Wang S, Liu H, et al. Protein kinase C-? negatively regulates T cell receptor-induced NF-?B activation by inhibiting the assembly of CARMA1 signalosome. J Biol Chem. 2012;287:20081-7 pubmed publisher
    ..of intracellular signaling, in which caspase recruitment domain-containing membrane-associated guanylate kinase 1 (CARMA1) is a crucial scaffold protein...
  36. Yang Y, Kelly P, Shaffer A, Schmitz R, Yoo H, Liu X, et al. Targeting Non-proteolytic Protein Ubiquitination for the Treatment of Diffuse Large B Cell Lymphoma. Cancer Cell. 2016;29:494-507 pubmed publisher
    ..SMAC mimetics target cIAP1/2 for destruction, and consequently suppress NF-?B and selectively kill BCR-dependent ABC DLBCL lines, supporting their clinical evaluation in patients with ABC DLBCL. ..
  37. Pérez de Diego R, Sánchez Ramón S, López Collazo E, Martínez Barricarte R, Cubillos Zapata C, Ferreira Cerdán A, et al. Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity. J Allergy Clin Immunol. 2015;136:1139-49 pubmed publisher
    ..This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of each of the components of the CBM complex to human immunity. ..
  38. Giallourakis C, Cao Z, Green T, Wachtel H, Xie X, Lopez Illasaca M, et al. A molecular-properties-based approach to understanding PDZ domain proteins and PDZ ligands. Genome Res. 2006;16:1056-72 pubmed
    ..These results provide insight into the diverse roles of PDZ-ligand complexes in cellular signaling and provide a computational framework for the genome-wide evaluation of PDZ complexes. ..
  39. Douanne T, Gavard J, Bidère N. The paracaspase MALT1 cleaves the LUBAC subunit HOIL1 during antigen receptor signaling. J Cell Sci. 2016;129:1775-80 pubmed publisher
    Antigen-receptor-mediated activation of lymphocytes relies on a signalosome comprising CARMA1 (also known as CARD11), BCL10 and MALT1 (the CBM complex)...
  40. Fox L, Yannakou C, Ryland G, Lade S, Dickinson M, Campbell B, et al. Molecular Mechanisms of Disease Progression in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type during Ibrutinib Therapy. Int J Mol Sci. 2018;19: pubmed publisher
    ..We describe the first case of novel genomic changes of PCDLBCL-LT that occurred while on ibrutinib, providing important mechanistic insights into both pathogenesis and drug resistance. ..
  41. Ginster S, Bardet M, Unterreiner A, Malinverni C, Renner F, Lam S, et al. Two Antagonistic MALT1 Auto-Cleavage Mechanisms Reveal a Role for TRAF6 to Unleash MALT1 Activation. PLoS ONE. 2017;12:e0169026 pubmed publisher
    ..Altogether, this study provides further insights into mechanisms that regulate the scaffolding and activation cycle of MALT1. It also emphasizes the reduced functional capacity of MALT1B as compared to MALT1A. ..
  42. Li J, Brieher W, Scimone M, Kang S, Zhu H, Yin H, et al. Caspase-11 regulates cell migration by promoting Aip1-Cofilin-mediated actin depolymerization. Nat Cell Biol. 2007;9:276-86 pubmed
    ..These data demonstrate a novel cell autonomous caspase-mediated mechanism that regulates actin dynamics and mammalian cell migration distinct from the receptor mediated Rho-Rac-Cdc42 pathway. ..
  43. Ramadas R, Roche M, Moon J, Ludwig T, Xavier R, Medoff B. CARMA1 is necessary for optimal T cell responses in a murine model of allergic asthma. J Immunol. 2011;187:6197-207 pubmed publisher
    b>CARMA1 is a lymphocyte-specific scaffold protein necessary for T cell activation. Deletion of CARMA1 prevents the development of allergic airway inflammation in a mouse model of asthma due to a defect in naive T cell activation...
  44. Brohl A, Stinson J, Su H, Badgett T, Jennings C, Sukumar G, et al. Germline CARD11 Mutation in a Patient with Severe Congenital B Cell Lymphocytosis. J Clin Immunol. 2015;35:32-46 pubmed publisher
    ..We now refer to these patients as having BENTA disease (B cell Expansion with NF-κB and T cell Anergy).
  45. Hu D, Wirasinha R, Goodnow C, Daley S. IL-2 prevents deletion of developing T-regulatory cells in the thymus. Cell Death Differ. 2017;24:1007-1016 pubmed publisher
    ..Our results distinguish two bottlenecks at which strongly self-reactive thymocytes undergo deletion or progress to the next stage of T-reg differentiation; Card11 regulates the first bottleneck and IL-2 regulates the second. ..
  46. Sprooten E, Fleming K, Thomson P, Bastin M, Whalley H, Hall J, et al. White matter integrity as an intermediate phenotype: exploratory genome-wide association analysis in individuals at high risk of bipolar disorder. Psychiatry Res. 2013;206:223-31 pubmed publisher
  47. Stepensky P, Keller B, Buchta M, Kienzler A, Elpeleg O, Somech R, et al. Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects. J Allergy Clin Immunol. 2013;131:477-85.e1 pubmed publisher
    ..This report discloses the crucial and nonredundant role of canonical NF-?B activation and specifically CARD11 in the antigen-specific immune response in human subjects. ..
  48. Karim Z, Hensch N, Qasim H, Alshbool F, Khasawneh F. Role of I?B kinase ? in regulating the remodeling of the CARMA1-Bcl10-MALT1 complex. Biochem Biophys Res Commun. 2018;500:268-274 pubmed publisher
    ..Thus, while the CARMA1, Bcl10, and MALT1 (CBM) complex is essential for triggering IKK/NF-?B activation upon platelet stimulation, the ..
  49. Hiemcke Jiwa L, Leguit R, Snijders T, Jiwa N, Kuiper J, de Weger R, et al. Molecular analysis in liquid biopsies for diagnostics of primary central nervous system lymphoma: Review of literature and future opportunities. Crit Rev Oncol Hematol. 2018;127:56-65 pubmed publisher
    ..Prioritization and refinements of this approach can be constructed based upon multidisciplinary collaboration as well as novel scientific insights. ..
  50. Wray Dutra M, Chawla R, Thomas K, Seymour B, Arkatkar T, Sommer K, et al. Activated CARD11 accelerates germinal center kinetics, promoting mTORC1 and terminal differentiation. J Exp Med. 2018;215:2445-2461 pubmed publisher
    ..While aCARD11 potently impacts GC responses, the rapid GC contraction suggests it requires collaboration with events that limit terminal differentiation to promote lymphoma. ..
  51. David L, Li Y, Ma J, Garner E, Zhang X, Wu H. Assembly mechanism of the CARMA1-BCL10-MALT1-TRAF6 signalosome. Proc Natl Acad Sci U S A. 2018;115:1499-1504 pubmed publisher
    The CARMA1-BCL10-MALT1 (CBM) signalosome is a central mediator of T cell receptor and B cell receptor-induced NF-?B signaling that regulates multiple lymphocyte functions...
  52. Morimoto K, Baba Y, Shinohara H, Kang S, Nojima S, Kimura T, et al. LRRK1 is critical in the regulation of B-cell responses and CARMA1-dependent NF-κB activation. Sci Rep. 2016;6:25738 pubmed publisher
    ..Furthermore, LRRK1 physically interacted and potently synergized with CARMA1 to enhance NF-κB activation...
  53. Gaide O, Martinon F, Micheau O, Bonnet D, Thome M, Tschopp J. Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10 phosphorylation and NF-kappaB activation. FEBS Lett. 2001;496:121-7 pubmed
    ..We have identified a novel CARD-containing protein and interaction partner of Bcl10, named Carma1. Carma1 is predominantly expressed in lymphocytes and represents a new member of the membrane-associated guanylate ..
  54. Lam L, Davis R, Ngo V, Lenz G, Wright G, Xu W, et al. Compensatory IKKalpha activation of classical NF-kappaB signaling during IKKbeta inhibition identified by an RNA interference sensitization screen. Proc Natl Acad Sci U S A. 2008;105:20798-803 pubmed publisher
    ..These results suggest that therapy for ABC DLBCL may be improved by targeting both IKKalpha and IKKbeta, possibly through CARD11 inhibition. ..
  55. Park J, Park H. Crystallization and preliminary X-ray crystallographic studies of the CARD domain of human CARMA1. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013;69:435-7 pubmed publisher
    The CARMA1 signalosome, which is composed of CARMA1 [caspase recruitment domain (CARD) containing MAGUK protein 1], BCL10 (B-cell lymphoma 10) and MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1), is a molecular-..
  56. Hatchi E, Poalas K, Cordeiro N, N Debi M, Gavard J, Bidere N. Participation of the E3-ligase TRIM13 in NF-?B p65 activation and NFAT-dependent activation of c-Rel upon T-cell receptor engagement. Int J Biochem Cell Biol. 2014;54:217-22 pubmed publisher
    ..We further observed that c-Rel induction was diminished without TRIM13, as NFAT activation was compromised. These results unveil that TRIM13 is a selective regulator of p65 and of c-Rel activation. ..
  57. Letendre K, Donnadieu E, Moses M, Cannon J. Bringing statistics up to speed with data in analysis of lymphocyte motility. PLoS ONE. 2015;10:e0126333 pubmed publisher
    ..Here, we compare the motility of WT T cell versus PKC?-/-, CARMA1-/-, CCR7-/-, and PTX-treated T cells...
  58. Shinohara H, Yasuda T, Kurosaki T. TAK1 adaptor proteins, TAB2 and TAB3, link the signalosome to B-cell receptor-induced IKK activation. FEBS Lett. 2016;590:3264-9 pubmed publisher
    ..of TAB3, coupling of ubiquitin conjugation to ER degradation, coiled-coil, and zinc finger domains blocked IKK activation and association with CARMA1. Thus, TAB2 and TAB3 connect signaling molecules that activate IKK in BCR signaling.
  59. Brenner D, Brechmann M, Röhling S, Tapernoux M, Mock T, Winter D, et al. Phosphorylation of CARMA1 by HPK1 is critical for NF-kappaB activation in T cells. Proc Natl Acad Sci U S A. 2009;106:14508-13 pubmed publisher
    ..Here, we show that HPK1-mediated NF-kappaB activation is dependent on the adaptor protein CARMA1. HPK1 interacts with CARMA1 in a TCR stimulation-dependent manner and phosphorylates the linker region of CARMA1...
  60. Kojo S, Elly C, Harada Y, Langdon W, Kronenberg M, Liu Y. Mechanisms of NKT cell anergy induction involve Cbl-b-promoted monoubiquitination of CARMA1. Proc Natl Acad Sci U S A. 2009;106:17847-51 pubmed publisher
    ..Cbl-b binds and promotes monoubiquitination to CARMA1, a critical signaling molecule in NFkappaB activation...
  61. Yang Y, Lu Y, Espejo A, Wu J, Xu W, Liang S, et al. TDRD3 is an effector molecule for arginine-methylated histone marks. Mol Cell. 2010;40:1016-23 pubmed publisher
    ..Furthermore, ChIP-seq analysis of TDRD3 reveals that it is predominantly localized to transcriptional start sites. Thus, TDRD3 is an effector molecule that promotes transcription by binding methylarginine marks on histone tails...
  62. Li S, Yang X, Shao J, Shen Y. Structural insights into the assembly of CARMA1 and BCL10. PLoS ONE. 2012;7:e42775 pubmed publisher
    The CBM complex (CARMA1, BCL10 and MALT1) plays a crucial role in B and T lymphocyte activation...
  63. Liu F, Karube K, Kato H, Arita K, Yoshida N, Yamamoto K, et al. Mutation analysis of NF-?B signal pathway-related genes in ocular MALT lymphoma. Int J Clin Exp Pathol. 2012;5:436-41 pubmed
    ..Genetic or epigenetic alterations in other genes are likely to be relevant in pathogenesis of OAL case without A20 loss. ..
  64. Hara H, Yokosuka T, Hirakawa H, Ishihara C, Yasukawa S, Yamazaki M, et al. Clustering of CARMA1 through SH3-GUK domain interactions is required for its activation of NF-κB signalling. Nat Commun. 2015;6:5555 pubmed publisher
    b>CARMA1-mediated NF-κB activation controls lymphocyte activation through antigen receptors and survival of some malignant lymphomas...
  65. Pon J, Wong J, Saberi S, Alder O, Moksa M, Grace Cheng S, et al. MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation. Nat Commun. 2015;6:7953 pubmed publisher
    ..The K4E and D83V mutations decrease MEF2B DNA binding. In conclusion, our map of the MEF2B regulome connects MEF2B to drivers of oncogenesis. ..
  66. Nagel D, Bognar M, Eitelhuber A, Kutzner K, Vincendeau M, Krappmann D. Combinatorial BTK and MALT1 inhibition augments killing of CD79 mutant diffuse large B cell lymphoma. Oncotarget. 2015;6:42232-42 pubmed publisher
    ..However, mutations in BTK or in downstream components such as CARMA1/CARD11 can render lymphomas Ibrutinib resistant...
  67. Vallois D, Dobay M, Morin R, Lemonnier F, Missiaglia E, Juilland M, et al. Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell-derived lymphomas. Blood. 2016;128:1490-502 pubmed publisher
    ..Thus, targeting of TCR-related events may hold promise for the treatment of TFH-derived lymphomas. ..
  68. Gong C, Sun S, Liu B, Wang J, Chen X. Identification of potential therapeutic target genes, key miRNAs and mechanisms in oral lichen planus by bioinformatics analysis. Arch Oral Biol. 2017;78:122-128 pubmed publisher
    ..The genes such as TNF, CARD11, MRP genes and CCND1 may be potential therapeutic target genes in OLP. MiR-548a-2 and miR-302 may play important roles in OLP development. ..
  69. Howes A, O Sullivan P, Breyer F, Ghose A, Cao L, Krappmann D, et al. Psoriasis mutations disrupt CARD14 autoinhibition promoting BCL10-MALT1-dependent NF-κB activation. Biochem J. 2016;473:1759-68 pubmed publisher
    ..Our results establish the mechanism whereby gain-of-function CARD14 variants, which induce psoriatic disease in affected individuals, activate pro-inflammatory signalling. ..
  70. Roncagalli R, Cucchetti M, Jarmuzynski N, Gregoire C, Bergot E, Audebert S, et al. The scaffolding function of the RLTPR protein explains its essential role for CD28 co-stimulation in mouse and human T cells. J Exp Med. 2016;213:2437-2457 pubmed
    ..followed by mass spectrometry analysis, we showed that RLTPR acts as a scaffold, bridging CD28 to the CARD11/CARMA1 cytosolic adaptor and to the NF-?B signaling pathway, and identified proteins not found before within the CD28 ..
  71. Paul J, Soujon M, Wengner A, Zitzmann Kolbe S, Sturz A, Haike K, et al. Simultaneous Inhibition of PI3Kδ and PI3Kα Induces ABC-DLBCL Regression by Blocking BCR-Dependent and -Independent Activation of NF-κB and AKT. Cancer Cell. 2017;31:64-78 pubmed publisher
    ..A combination of ibrutinib with the PI3Kα/δ inhibitor copanlisib produced a sustained complete response in vivo in CD79Bmut/MYD88mut ABC-DLBCL models. ..
  72. Moody S, Escudero Ibarz L, Wang M, Clipson A, Ochoa Ruiz E, Dunn Walters D, et al. Significant association between TNFAIP3 inactivation and biased immunoglobulin heavy chain variable region 4-34 usage in mucosa-associated lymphoid tissue lymphoma. J Pathol. 2017;243:3-8 pubmed publisher
    ..Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. ..
  73. Karim Z, Vemana H, Khasawneh F. MALT1-ubiquitination triggers non-genomic NF-κB/IKK signaling upon platelet activation. PLoS ONE. 2015;10:e0119363 pubmed publisher
    ..Thus, our data demonstrate that MALT1 ubiquitination is critical for the engagement of CBM and IKK complexes, thereby directing platelet signals to the NF-κB pathway. ..
  74. Pastore A, Jurinovic V, Kridel R, Hoster E, Staiger A, Szczepanowski M, et al. Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol. 2015;16:1111-1122 pubmed publisher
    ..Deutsche Krebshilfe, Terry Fox Research Institute. ..
  75. Cohen J. Primary Immunodeficiencies Associated with EBV Disease. Curr Top Microbiol Immunol. 2015;390:241-65 pubmed publisher
    ..Identification of proteins important for control of EBV may help to identify new targets for immunosuppressive therapies. ..
  76. Arjunaraja S, Nosé B, Sukumar G, Lott N, Dalgard C, Snow A. Intrinsic Plasma Cell Differentiation Defects in B Cell Expansion with NF-?B and T Cell Anergy Patient B Cells. Front Immunol. 2017;8:913 pubmed publisher
    B cell Expansion with NF-?B and T cell Anergy (BENTA) disease is a novel B cell lymphoproliferative disorder caused by germline, gain-of-function mutations in the lymphocyte scaffolding protein CARD11, which drives constitutive NF-?B ..
  77. Yang Y, Yang C, Chan W, Wang Z, Deibel K, Pomerantz J. Molecular Determinants of Scaffold-induced Linear Ubiquitinylation of B Cell Lymphoma/Leukemia 10 (Bcl10) during T Cell Receptor and Oncogenic Caspase Recruitment Domain-containing Protein 11 (CARD11) Signaling. J Biol Chem. 2016;291:25921-25936 pubmed
    ..Our results define molecular determinants that control the production of Lin(Ub)n-Bcl10, an important signaling intermediate in TCR and oncogenic CARD11 signaling. ..
  78. Qiao Q, Yang C, Zheng C, Fontan L, David L, Yu X, et al. Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-induced filamentous assembly. Mol Cell. 2013;51:766-79 pubmed publisher
    The CARMA1/Bcl10/MALT1 (CBM) signalosome mediates antigen receptor-induced NF-?B signaling to regulate multiple lymphocyte functions...
  79. Takeuchi T, Yamaguchi M, Kobayashi K, Miyazaki K, Tawara I, Imai H, et al. MYD88, CD79B, and CARD11 gene mutations in CD5-positive diffuse large B-cell lymphoma. Cancer. 2017;123:1166-1173 pubmed publisher
    ..CARD11 mutations are rare in patients with CD5+ DLBCL. Cancer 2017;123:1166-1173. © 2016 American Cancer Society. ..
  80. Kim M, Yoo N, Lee S. Very low mutation frequency of exons 5-9 in the CARD11 gene from 186 adult acute leukemia and 31 multiple myeloma samples. Leuk Res. 2011;35:e46-7 pubmed publisher
  81. Clipman S, Henderson Frost J, Fu K, Bern C, Flores J, Gilman R. Genetic association study of NLRP1, CARD, and CASP1 inflammasome genes with chronic Chagas cardiomyopathy among Trypanosoma cruzi seropositive patients in Bolivia. PLoS ONE. 2018;13:e0192378 pubmed publisher
    ..060). Although limited by sample size, the study results suggest variations in the inflammasome, particularly in NLRP1 and CARD11, may be associated with CCC. ..
  82. Srivastava R, Burbach B, Shimizu Y. NF-kappaB activation in T cells requires discrete control of IkappaB kinase alpha/beta (IKKalpha/beta) phosphorylation and IKKgamma ubiquitination by the ADAP adapter protein. J Biol Chem. 2010;285:11100-5 pubmed publisher
    ..engagement of the antigen-specific T cell receptor involves protein kinase C-theta-dependent assembly of the CARMA1-BCL10-MALT1 (CBM) signalosome, which coordinates downstream activation of IkappaB kinase (IKK)...
  83. Tampella G, Baronio M, Vitali M, Soresina A, Badolato R, Giliani S, et al. Evaluation of CARMA1/CARD11 and Bob1 as candidate genes in common variable immunodeficiency. J Investig Allergol Clin Immunol. 2011;21:348-53 pubmed
    ..Animal models for 2 genes involved in B-cell development, namely CARMA1/CARD11 and Bob1, develop an immunological phenotype similar to that seen in CVID, with low immunoglobulin serum ..
  84. Fuchs S, Rensing Ehl A, Pannicke U, Lorenz M, Fisch P, Jeelall Y, et al. Omenn syndrome associated with a functional reversion due to a somatic second-site mutation in CARD11 deficiency. Blood. 2015;126:1658-69 pubmed publisher
    ..This first observation of OS in a patient with a T-cell activation defect suggests that severely defective T-cell development or homeostatic proliferation in a lymphopenic environment are not required for this severe immunopathology. ..
  85. Grommes C, Pastore A, Palaskas N, Tang S, Campos C, Schartz D, et al. Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma. Cancer Discov. 2017;7:1018-1029 pubmed publisher
    ..i>Cancer Discov; 7(9); 1018-29. ©2017 AACR.See related commentary by Lakshmanan and Byrd, p. 940This article is highlighted in the In This Issue feature, p. 920. ..
  86. Chen Y, Yang W, Meng Q, Zhong Y. [Correlation between the expressions of CARMA1 gene and MUM1 and its significance in diffuse large B cell lymphoma]. Zhonghua Xue Ye Xue Za Zhi. 2011;32:236-40 pubmed
    To determine the correlation between the expression of CARMA1 mRNA and MUM1 protein, as well as its effects on clinicopathological features and prognosis of diffuse large B cell lymphoma (DLBCL)...
  87. Jono H, Lim J, Xu H, Li J. PKC? synergizes with TLR-dependent TRAF6 signaling pathway to upregulate MUC5AC mucin via CARMA1. PLoS ONE. 2012;7:e31049 pubmed publisher
    CARD-containing MAGUK protein 1 (CARMA1) plays a crucial role in regulating adaptive immune responses upon T-cell receptor (TCR) activation in T cells...
  88. Watt S, Purdie K, den Breems N, Dimon M, Arron S, McHugh A, et al. Novel CARD11 Mutations in Human Cutaneous Squamous Cell Carcinoma Lead to Aberrant NF-κB Regulation. Am J Pathol. 2015;185:2354-63 pubmed publisher
    ..In addition, we identified CARD11 mutations in peritumoral and sun-exposed skin, suggesting that CARD11-mediated alterations in NF-κB signaling may be an early event in the development of cSCC. ..
  89. Langel F, Jain N, Rossman J, Kingeter L, Kashyap A, Schaefer B. Multiple protein domains mediate interaction between Bcl10 and MALT1. J Biol Chem. 2008;283:32419-31 pubmed publisher
    ..Moreover, the Bcl10-MALT1 interaction is the second reported example of interactions between a CARD and a non-CARD protein region, which suggests that many signaling cascades may utilize CARD interactions with non-CARD domains. ..
  90. Bognar M, Vincendeau M, Erdmann T, Seeholzer T, Grau M, Linnemann J, et al. Oncogenic CARMA1 couples NF-κB and β-catenin signaling in diffuse large B-cell lymphomas. Oncogene. 2016;35:4269-81 pubmed publisher
    ..Recurrent oncogenic mutations are found in the scaffold protein CARMA1 (CARD11) that connects B-cell receptor (BCR) signaling to the canonical NF-κB pathway...
  91. Narayan P, Holt B, Tosti R, Kane L. CARMA1 is required for Akt-mediated NF-kappaB activation in T cells. Mol Cell Biol. 2006;26:2327-36 pubmed
    ..Recent studies have shown that the CARMA1, Bcl10, and MALT1 proteins are critical for coupling the common elements of the NF-kappaB pathway to the T-cell ..
  92. Bu R, Bavi P, Abubaker J, Jehan Z, Al Haqawi W, Ajarim D, et al. Role of nuclear factor-κB regulators TNFAIP3 and CARD11 in Middle Eastern diffuse large B-cell lymphoma. Leuk Lymphoma. 2012;53:1971-7 pubmed publisher