Letter to the Editor
A toxic palmitoylation of Cdc42 enhances NF-κB signaling and drives a severe autoinflammatory syndrome

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Cited by (28)

  • CDC42 regulates PYRIN inflammasome assembly

    2022, Cell Reports
    Citation Excerpt :

    These mutations specifically impacted the C-terminal CAAX tail of CDC42, which is usually isoprenylated to facilitate association with and localization to the plasma membrane. CDC42 R186C is aberrantly palmitated and sequestered at the Golgi membrane30 and was shown to induce hyperactivation of the PYRIN inflammasome pathway upon treatment with RhoA inhibitors.31 Of note, the CDC42 R186C-mediated effect on PYRIN was independent of its GTPase activity.31

  • Mutations at the C-terminus of CDC42 cause distinct hematopoietic and autoinflammatory disorders

    2022, Journal of Allergy and Clinical Immunology
    Citation Excerpt :

    In contrast, in patients with p.R186C, cytopenia is in general not responsive to IL-1 inhibition. Available data suggest that the p.R186C substitution triggers overactivation of several inflammatory pathways with increased production of IL-1, IL-6, TNF, IL-18, IFN-γ, and CXCL9.8,9,12 IL-1 overproduction appears to be responsible for some of the autoinflammatory features; overproduction of IL-18 drives IFN-γ and HLH, which may be fatal.8

  • Inborn errors of immunity with atopic phenotypes: A practical guide for allergists

    2021, World Allergy Organization Journal
    Citation Excerpt :

    More recently, additional reports further expanded the clinical spectrum of human diseases caused by inherited CDC42 mutations.102–108 Of note, He et al and Bekhouche et al reported on 2 patients with the p.Arg186Cys mutation, dysmorphism, and NOCARH along with elevation in total serum IgE.107,108 Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is a X-linked recessive IEI that manifests in infancy with enteropathy, eczema, and severe autoimmune manifestations, including cytopenias, type 1 diabetes mellitus, autoimmune hepatitis, nephropathy, and myopathy.109,110

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Supported by INSERM, CNRS, Université de Paris, Association pour la Recherche contre le Cancer (to J.D.), Ligue Contre le Cancer (to S.E.M.), Société Française de Dermatologie (to A.S., C.B., and J.D.), Agence Nationale de la Recherche (RIDES to A.S., J.D., and J.C.), the European Union Horizon 2020 Marie Skłodowska-Curie research and innovation program (MSCA-ITN-2015-675407 to S.E.M.), Institut Pasteur, the Région Ile de France and the Fondation pour la Recherche Médicale (J.C. and D.L.).

Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

These authors contributed equally to this work as first authors.

These authors contributed equally to this work.

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