card signaling adaptor proteins


Summary: A family of intracellular signaling adaptor proteins that contain CASPASE ACTIVATION AND RECRUITMENT DOMAINS (CARD). They play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.

Top Publications

  1. Di Simone N, Di Nicuolo F, Marana R, Castellani R, Ria F, Veglia M, et al. Synthetic PreImplantation Factor (PIF) prevents fetal loss by modulating LPS induced inflammatory response. PLoS ONE. 2017;12:e0180642 pubmed publisher
    ..Given that synthetic PIF is currently tested in autoimmune diseases of non-pregnant subjects (, NCT02239562), therapeutic approach during pregnancy can be envisioned. ..
  2. Montesinos Rongen M, Godlewska E, Brunn A, Wiestler O, Siebert R, Deckert M. Activating L265P mutations of the MYD88 gene are common in primary central nervous system lymphoma. Acta Neuropathol. 2011;122:791-2 pubmed publisher
  3. Nikbakht M, Jha A, Malekzadeh K, Askari M, Mohammadi S, Marwaha R, et al. Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among North Indian population. Exp Oncol. 2017;39:57-64 pubmed
    ..This abnormality occurs in leukemogenesis and it may be used as a biomarker and for predicting the prognosis of ALL. ..
  4. Parrish A, Freel C, Kornbluth S. Cellular mechanisms controlling caspase activation and function. Cold Spring Harb Perspect Biol. 2013;5: pubmed publisher
    ..It is likely that continued examination of these processes will reveal new mechanisms of caspase regulation with implications well beyond control of apoptotic cell death. ..
  5. Schimmack G, Eitelhuber A, Vincendeau M, Demski K, Shinohara H, Kurosaki T, et al. AIP augments CARMA1-BCL10-MALT1 complex formation to facilitate NF-κB signaling upon T cell activation. Cell Commun Signal. 2014;12:49 pubmed publisher
    ..Thereby, AIP promoted optimal IKK/NF-κB signaling and IL-2 production in response to TCR/CD28 co-stimulation. Our data demonstrate that AIP acts as a positive regulator of NF-κB signaling upon T cell activation. ..
  6. Joosten L, Ea H, Netea M, Busso N. Interleukin-1? activation during acute joint inflammation: a limited role for the NLRP3 inflammasome in vivo. Joint Bone Spine. 2011;78:107-10 pubmed publisher
  7. Fontalba A, Gutierrez O, Llorca J, Mateo I, Vázquez Higuera J, Berciano J, et al. Gene-gene interaction between CARD8 and interleukin-6 reduces Alzheimer's disease risk. J Neurol. 2009;256:1184-6 pubmed publisher
  8. Daley D, Mani V, Mohan N, Akkad N, Pandian G, Savadkar S, et al. NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma. J Exp Med. 2017;214:1711-1724 pubmed publisher
    ..Similarly, transfer of PDA-entrained macrophages or T cells from NLRP3-/- hosts was protective. These data suggest that targeting NLRP3 holds the promise for the immunotherapy of PDA. ..
  9. Wang X, Wang W, Lin Z, Wang X, Li T, Yu J, et al. CARD9 mutations linked to subcutaneous phaeohyphomycosis and TH17 cell deficiencies. J Allergy Clin Immunol. 2014;133:905-8.e3 pubmed publisher

More Information


  1. Oruganti S, Torres D, Krebsbach S, Asperti Boursin F, Winters J, Matlawska Wasowska K, et al. CARMA1 is a novel regulator of T-ALL disease and leukemic cell migration to the CNS. Leukemia. 2017;31:255-258 pubmed publisher
  2. Lamkanfi M, Dixit V. The inflammasomes. PLoS Pathog. 2009;5:e1000510 pubmed publisher
  3. Mascarenhas D, Cerqueira D, Pereira M, Castanheira F, Fernandes T, Manin G, et al. Inhibition of caspase-1 or gasdermin-D enable caspase-8 activation in the Naip5/NLRC4/ASC inflammasome. PLoS Pathog. 2017;13:e1006502 pubmed publisher
    ..Our data suggest that caspase-8 activation in the Naip5/NLRC4/ASC inflammasome enable induction of cell death when caspase-1 or gasdermin-D is suppressed. ..
  4. Zhang K, Song W, Li D, Yan J, Chen Y, Qi H, et al. The Association between Polymorphism of CARD8 rs2043211 and Susceptibility to Arteriosclerosis Obliterans in Chinese Han Male Population. Cell Physiol Biochem. 2017;41:173-180 pubmed publisher
    ..525, 95%CI1.158-2.009, P = 0.003). Our finding suggests that the polymorphism of CARD8 rs2043211 is probably associated with the development of ASO in Chinese Han male population. ..
  5. Tschope C, Muller I, Xia Y, Savvatis K, Pappritz K, Pinkert S, et al. NOD2 (Nucleotide-Binding Oligomerization Domain 2) Is a Major Pathogenic Mediator of Coxsackievirus B3-Induced Myocarditis. Circ Heart Fail. 2017;10: pubmed publisher
    ..NOD2 is an important mediator in the viral uptake and inflammatory response during the pathogenesis of CVB3 myocarditis. ..
  6. Ghosh S, Wallerath C, Covarrubias S, Hornung V, Carpenter S, Fitzgerald K. The PYHIN Protein p205 Regulates the Inflammasome by Controlling Asc Expression. J Immunol. 2017;199:3249-3260 pubmed publisher
    ..Together, these findings suggest that p205 controls expression of Asc mRNA to regulate inflammasome responses. These findings expand on our understanding of immune-regulatory roles for the PYHIN protein family. ..
  7. Oosting M, Buffen K, Malireddi S, Sturm P, Verschueren I, Koenders M, et al. Murine Borrelia arthritis is highly dependent on ASC and caspase-1, but independent of NLRP3. Arthritis Res Ther. 2012;14:R247 pubmed publisher
    ..Based on present results indicating that IL-1 is one of the major mediators in Lyme arthritis, there is a rationale to propose that neutralizing IL-1 activity may also have beneficial effects in chronic Lyme arthritis. ..
  8. Glocker E, Grimbacher B. Mucosal antifungal defence: IL-17 signalling takes centre stage. Immunol Cell Biol. 2011;89:823-5 pubmed publisher
  9. Yi P, Wang Z, Feng Q, Chou C, Pintilie G, Shen H, et al. Structural and Functional Impacts of ER Coactivator Sequential Recruitment. Mol Cell. 2017;67:733-743.e4 pubmed publisher
    ..This study reveals a structural role for a coactivator sequential recruitment and biochemical process in ER-mediated transcription. ..
  10. Sugiura K. Autoinflammatory diseases in dermatology: DITRA and CAMPS. Nihon Rinsho Meneki Gakkai Kaishi. 2017;40:169-173 pubmed publisher
    ..GPP without PsV and PRP type V are representative diseases of DITRA and CAMPS, respectively. ..
  11. Liu F, Ma F, Wang Y, Hao L, Zeng H, Jia C, et al. PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis. Nat Cell Biol. 2017;19:1358-1370 pubmed publisher
    ..Collectively, the CARM1-PKM2 axis serves as a metabolic reprogramming mechanism in tumorigenesis, and inhibiting PKM2 methylation generates metabolic vulnerability to InsP3R-dependent mitochondrial functions. ..
  12. Uchiyama R, Yonehara S, Taniguchi S, Ishido S, Ishii K, Tsutsui H. Inflammasome and Fas-Mediated IL-1? Contributes to Th17/Th1 Cell Induction in Pathogenic Bacterial Infection In Vivo. J Immunol. 2017;199:1122-1130 pubmed publisher
    ..This study provides a deeper understanding of the molecular mechanisms underlying Th17/Th1 induction during pathogenic microbial infections in vivo. ..
  13. Murata K, Motomura Y, Tanaka T, Kanno S, Yano T, Onimaru M, et al. Calcineurin inhibitors exacerbate coronary arteritis via the MyD88 signalling pathway in a murine model of Kawasaki disease. Clin Exp Immunol. 2017;190:54-67 pubmed publisher
    ..Particular attention should be paid to the development of coronary artery lesions when using CNIs to treat refractory KD. ..
  14. Zhu S, Ding S, Wang P, Wei Z, Pan W, Palm N, et al. Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells. Nature. 2017;546:667-670 pubmed publisher
    ..Our study highlights an important innate immune signalling pathway that functions in intestinal epithelial cells and may present useful targets in the modulation of host defences against viral pathogens. ..
  15. Eren E, Berber M, Ozören N. NLRC3 protein inhibits inflammation by disrupting NALP3 inflammasome assembly via competition with the adaptor protein ASC for pro-caspase-1 binding. J Biol Chem. 2017;292:12691-12701 pubmed publisher
    ..In conclusion, we show here that, besides its role in the inhibition of the NF-?B pathway, NLRC3 interferes with the assembly and activity of the NALP3 inflammasome complex by competing with ASC for pro-caspase-1 binding. ..
  16. Bivik C, Verma D, Winge M, Lieden A, Bradley M, Rosdahl I, et al. Genetic variation in the inflammasome and atopic dermatitis susceptibility. J Invest Dermatol. 2013;133:2486-2489 pubmed publisher
  17. Donath M. Inflammation as a sensor of metabolic stress in obesity and type 2 diabetes. Endocrinology. 2011;152:4005-6 pubmed publisher
  18. Scholz H, Eder C. Lysophosphatidylcholine activates caspase-1 in microglia via a novel pathway involving two inflammasomes. J Neuroimmunol. 2017;310:107-110 pubmed publisher
    ..Furthermore, knockdown of inflammasome NLRC4 inhibited LPC-stimulated caspase-1 activity in microglia, suggesting the requirement of two inflammasomes for optimal caspase-1 activity. ..
  19. Broderick L, Hoffman H. cASCading specks. Nat Immunol. 2014;15:698-700 pubmed publisher
  20. Ito S, Hara Y, Kubota T. CARD8 is a negative regulator for NLRP3 inflammasome, but mutant NLRP3 in cryopyrin-associated periodic syndromes escapes the restriction. Arthritis Res Ther. 2014;16:R52 pubmed publisher
    ..Until specific stimuli activate NLRP3, CARD8 holds NLRP3, and is supposed to prevent activation by subtle stimuli. However, CAPS-associated mutant NLRP3 is unable to bind with CARD8, which might be relevant to the pathogenesis of CAPS. ..
  21. Ma C, Stinson J, Zhang Y, Abbott J, Weinreich M, Hauk P, et al. Germline hypomorphic CARD11 mutations in severe atopic disease. Nat Genet. 2017;49:1192-1201 pubmed publisher
    ..Our findings indicate that a single hypomorphic mutation in CARD11 can cause potentially correctable cellular defects that lead to atopic dermatitis. ..
  22. Xie S, Guo C, Chi Z, Huang B, Wu Y, Wang D, et al. A rapid administration of GW4064 inhibits the NLRP3 inflammasome activation independent of farnesoid X receptor agonism. FEBS Lett. 2017;591:2836-2847 pubmed publisher
    ..These results not only necessitate cautious interpretation of the biological function of GW4064 as an FXR agonist, but also provide a potential therapeutic approach using GW4064 in the treatment of NLRP3-related diseases. ..
  23. Mamantopoulos M, Ronchi F, Van Hauwermeiren F, Vieira Silva S, Yilmaz B, Martens L, et al. Nlrp6- and ASC-Dependent Inflammasomes Do Not Shape the Commensal Gut Microbiota Composition. Immunity. 2017;47:339-348.e4 pubmed publisher
  24. Hu G, Song P, Chen W, Qi S, Yu S, Du C, et al. Cirtical role for Salmonella effector SopB in regulating inflammasome activation. Mol Immunol. 2017;90:280-286 pubmed publisher
    ..Furthermore, inhibition of Akt signaling induced enhanced inflammasome activation. These results revealed a novel role in inhibition of NLRC4 inflammasome for Salmonella effector SopB. ..
  25. Bergmann H, Roth S, Pechloff K, Kiss E, Kuhn S, Heikenwalder M, et al. Card9-dependent IL-1? regulates IL-22 production from group 3 innate lymphoid cells and promotes colitis-associated cancer. Eur J Immunol. 2017;47:1342-1353 pubmed publisher
    ..Our results imply a Card9-controlled, ILC3-mediated mechanism regulating healthy and malignant IEC proliferation and demonstrates a role of Card9-mediated innate immunity in inflammation-associated carcinogenesis. ..