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Cited by 3NF-κB Signaling PathwaysImmune Response and InflammationImmunodeficiency and Autoimmune Disorders

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Chimeric and mutant CARD9 constructs enable analyses of conserved and diverged autoinhibition mechanisms in the CARD‐CC protein family

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Staal, Jens, Driege, Yasmine, Van Gaever, Femke, Steels, Jill, Beyaert, Rudi·2024·The FEBS Journal
DOI 10.1111/febs.17035

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Abstract

Caspase recruitment domain‐containing protein (CARD)9, CARD10, CARD11, and CARD14 all belong to the CARD‐coiled coil (CC) protein family and originated from a single common ancestral protein early in vertebrate evolution. All four proteins form CARD‐CC/BCL10/MALT1 (CBM) complexes leading to nuclear factor‐kappa‐B (NF‐κB) activation after upstream phosphorylation by various protein kinase C (PKC) isoforms. CBM complex signaling is critical for innate and adaptive immunity, but aberrant activation can cause autoimmune or autoinflammatory diseases, or be oncogenic. CARD9 shows a superior auto‐inhibition compared with other CARD‐CC family proteins, with very low spontaneous activity when overexpressed in HEK293T cells. In contrast, the poor auto‐inhibition of other CARD‐CC family proteins, especially CARD10 (CARMA3) and CARD14 (CARMA2), is hampering characterization of upstream activators or activating mutations in overexpression studies. We grafted different domains from CARD10, 11, and 14 on CARD9 to generate chimeric CARD9 backbones for functional characterization of activating mutants using NF‐κB reporter gene activation in HEK293T cells as readout. CARD11 (CARMA1) activity was not further reduced by grafting on CARD9 backbones. The chimeric CARD9 approach was subsequently validated by using several known disease‐associated mutations in CARD10 and CARD14, and additional screening allowed us to identify several previously unknown activating natural variants in human CARD9 and CARD10. Using Genebass as a resource of exome‐based disease association statistics, we found that activated alleles of CARD9 correlate with irritable bowel syndrome (IBS), constipation, osteoarthritis, fibromyalgia, insomnia, anxiety, and depression, which can occur as comorbidities.

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References 114 · Cited by 3

Research works printed but not linked: 105

  1. 10.1016/j.molmed.2015.12.004 · DOI
  2. 10.3389/fimmu.2018.01136 · DOI
  3. 10.1007/s00018-015-2041-9 · DOI
  4. 10.7554/eLife.79826 · DOI · Paper page
  5. 10.3389/fimmu.2018.01927 · DOI
  6. 10.1038/s41577-018-0087-2 · DOI
  7. 10.3389/fimmu.2018.01539 · DOI
  8. 10.1111/febs.15210 · DOI
  9. 10.1016/j.ydbio.2021.07.013 · DOI
  10. 10.1111/febs.15522 · DOI
  11. 10.1186/1471-2148-10-93 · DOI
  12. 10.1016/j.molcel.2013.08.032 · DOI
  13. 10.1038/s41467-018-06573-8 · DOI
  14. 10.1074/jbc.M700169200 · DOI
  15. 10.1038/s41467-019-10953-z · DOI
  16. 10.1074/jbc.C000726200 · DOI
  17. 10.1074/jbc.M310599200 · DOI
  18. 10.1073/pnas.0601947103 · DOI
  19. 10.15252/embr.201642109 · DOI
  20. 10.1016/j.molcel.2019.12.020 · DOI
  21. 10.1016/j.csbj.2022.08.021 · DOI
  22. 10.3389/fimmu.2018.02695 · DOI
  23. 10.1021/bi101052d · DOI
  24. 10.1042/BCJ20160270 · DOI
  25. 10.1016/j.immuni.2005.09.014 · DOI
  26. 10.1016/j.cellimm.2018.11.001 · DOI
  27. 10.1016/j.jaci.2022.06.023 · DOI
  28. 10.1016/j.jaci.2012.11.050 · DOI
  29. 10.1016/j.jaci.2010.12.1081 · DOI
  30. 10.1038/ng.3898 · DOI
  31. 10.3389/fimmu.2019.02330 · DOI
  32. 10.1007/s10875-022-01387-2 · DOI
  33. 10.3389/fimmu.2018.02366 · DOI
  34. Ji C, 2021, The role and mechanism of CARD9 gene polymorphism in diseases, Biom J, 44, 560
  35. 10.3389/fimmu.2019.00130 · DOI
  36. 10.1016/j.jaci.2018.09.002 · DOI
  37. 10.1101/gad.1502507 · DOI
  38. 10.1016/S0092-8674(01)00189-1 · DOI
  39. 10.1038/s41423-020-0423-x · DOI
  40. 10.1002/mgg3.248 · DOI
  41. Zou Y, 2018, Analysis of CARD10 and CARD11 somatic mutations in patients with ovarian endometriosis, Oncol Lett, 16, 491
  42. 10.1007/s13238-017-0441-3 · DOI
  43. Vanneste D, 2022, CARD14 Signalling ensures cell survival and cancer associated gene expression in prostate cancer cells, Biomedicine, 10
  44. 10.1073/pnas.1205299110 · DOI
  45. 10.1007/s10875-014-0106-4 · DOI
  46. 10.3389/fimmu.2018.02239 · DOI
  47. 10.1016/j.jaad.2018.02.034 · DOI
  48. 10.1038/s41467-021-24573-z · DOI · Paper page
  49. MarlétazF TimoshevskayaN TimoshevskiyV SimakovO PareyE GavriouchkinaD SuzukiM KubokawaK BrennerS SmithJet al. (2023)The hagfish genome and the evolution of vertebrates. bioRxiv.10.1101/2023.04.17.537254[PREPRINT] · DOI
  50. 10.1002/j.1538-7305.1950.tb00463.x · DOI · Paper page
  51. 10.1111/j.1574-6941.2006.00060.x · DOI
  52. EvansR O'NeillM PritzelA AntropovaN SeniorA GreenT ŽídekA BatesR BlackwellS YimJet al. (2022)Protein complex prediction with AlphaFold‐Multimer.bioRxiv.10.1101/2021.10.04.463034[PREPRINT] · DOI
  53. 10.3389/fimmu.2018.02078 · DOI
  54. 10.1182/blood.2023020211 · DOI
  55. 10.1126/science.1153629 · DOI
  56. 10.1128/MCB.00850-12 · DOI
  57. 10.1084/jem.20120831 · DOI
  58. 10.1016/j.immuni.2011.11.015 · DOI
  59. 10.1016/j.ajhg.2012.03.012 · DOI
  60. 10.1016/j.ajhg.2012.03.013 · DOI
  61. 10.1111/bjd.12952 · DOI
  62. 10.1093/nar/gkaa1100 · DOI · Paper page
  63. 10.1016/j.xgen.2022.100168 · DOI · Paper page
  64. Khanijow V, 2015, Sleep dysfunction and gastrointestinal diseases, Gastroenterol Hepatol, 11, 817
  65. 10.1177/1756284820977402 · DOI
  66. 10.1053/j.gastro.2018.03.064 · DOI · Paper page
  67. 10.1038/s41586-020-2308-7 · DOI · Paper page
  68. 10.1002/humu.24309 · DOI
  69. 10.1126/science.adg7492 · DOI · Paper page
  70. 10.1136/annrheumdis-2022-222497 · DOI
  71. 10.1016/j.bbrc.2004.06.101 · DOI
  72. 10.1016/j.plasmid.2013.01.004 · DOI
  73. 10.1038/s41590-018-0112-4 · DOI · Paper page
  74. 10.1073/pnas.1105020108 · DOI
  75. 10.3389/fimmu.2018.02944 · DOI
  76. 10.1038/ng.952 · DOI · Paper page
  77. 10.1016/j.immuni.2015.10.005 · DOI
  78. 10.1073/pnas.1705748114 · DOI
  79. 10.1158/0008-5472.CAN-17-1089 · DOI
  80. 10.1002/ctm2.808 · DOI
  81. 10.4132/jptm.2021.10.15 · DOI
  82. 10.1084/jem.20202280 · DOI
  83. 10.1016/j.ccr.2012.11.003 · DOI
  84. 10.1162/0024094041724472 · DOI
  85. 10.2144/01314bm02 · DOI
  86. 10.1093/bioinformatics/btab253 · DOI
  87. 10.1038/s41389-021-00321-2 · DOI
  88. 10.20897/ejsa.201701 · DOI
  89. 10.1016/j.immuni.2018.05.012 · DOI · Paper page
  90. 10.15252/embr.201949237 · DOI
  91. 10.1016/j.yexmp.2019.104286 · DOI
  92. 10.1038/onc.2015.493 · DOI
  93. 10.1126/sciimmunol.abi4425 · DOI
  94. 10.7554/eLife.56720 · DOI
  95. 10.1165/rcmb.2017-0181OC · DOI
  96. 10.1016/j.bbrc.2021.10.013 · DOI
  97. 10.3389/fimmu.2022.1057980 · DOI
  98. 10.1093/bioinformatics/bts091 · DOI
  99. ZhangG ElliotM HuY DrobotV StaalJ&YiY(2022)BioArchLinux: bioinformatics community with arch Linux. InBioinformatics Open Source Conference. Open Bioinformatics Foundation.
  100. 10.1093/nar/gkab314 · DOI · Paper page
  101. 10.2144/btn-2019-0014 · DOI
  102. 10.1016/0092-8674(86)90760-9 · DOI
  103. 10.1074/jbc.271.46.28745 · DOI
  104. 10.2307/2331554 · DOI · Paper page
  105. 10.1111/j.1462-5822.2007.00901.x · DOI

Metadata

Authors
Staal, J., Driege, Y., Van Gaever, F., Steels, J., & Beyaert, R.
Affiliations
  • Ghent University (BE)
  • Unit of Molecular Signal Transduction in Inflammation VIB‐UGent Center for Inflammation Research Belgium
Corresponding author
Staal, Jens
ORCID
Venue
The FEBS Journal
Publisher
Wiley
Published
2023-12-25
Volume
291
Issue
6
Pages
1220-1245
ISSN
  • 1742-464X (ISSN-L)
  • 1742-4658
DOI
10.1111/febs.17035
OpenAlex
W4389802450
Cited by
3
References
114
Citations by year
2025: 2 · 2024: 1
FWCI
0.38
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • FEBS Journal (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
Funders
  • Fonds Wetenschappelijk Onderzoek (3G0I1422, 3G086521)
  • Universiteit Gent (01G00419)
  • Vlaamse regering
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
Keywords
CARD9, CARD10, CARD11, CARD14, autoinhibition, chimeric constructs, CBM complex, NF-κB activation, protein kinase C phosphorylation, activating mutations, disease-associated variants, irritable bowel syndrome, comorbidities, innate immunity
MeSH terms
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein, Guanylate Cyclase, Humans, Membrane Proteins, Protein Kinase C, Signal Transduction, NF-kappa B, Apoptosis Regulatory Proteins, CARD Signaling Adaptor Proteins, HEK293 Cells

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