ArticleBlood2006
Impaired dendritic-cell function in ectodermal dysplasia with immune deficiency is linked to defective NEMO ubiquitination.
Article in Blood, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Antibody deficiency associated with an inherited autosomal dominant mutation in TWEAK.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Targeting ubiquitin signaling for cancer immunotherapy.Signal transduction and targeted therapy · 2021Review
- Importance of Deubiquitination in Macrophage-Mediated Viral Response and Inflammation.International journal of molecular sciences · 2020Review
- The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.Oncotarget · 2017Article
- Teuvincenone F Suppresses LPS-Induced Inflammation and NLRP3 Inflammasome Activation by Attenuating NEMO Ubiquitination.Frontiers in pharmacology · 2017Article
- Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4+ T cells into distinct effector subsets.The Journal of experimental medicine · 2016Article
- Ubiquitin signaling in immune responses.Cell research · 2016Review
- CYLD and the NEMO Zinc Finger Regulate Tumor Necrosis Factor Signaling and Early Embryogenesis.The Journal of biological chemistry · 2015Article
- Rare mendelian primary immunodeficiency diseases associated with impaired NF-κB signaling.Genes and immunity · 2015Review
- Correlating interleukin-12 stimulated interferon-γ production and the absence of ectodermal dysplasia and anhidrosis (EDA) in patients with mutations in NF-κB essential modulator (NEMO).Journal of clinical immunology · 2014Article
- Estradiol downregulates NF-κb translocation by Ikbkg transcriptional repression in dendritic cells.Genes and immunity · 2013Article
- Defective nuclear IKKα function in patients with ectodermal dysplasia with immune deficiency.The Journal of clinical investigation · 2012Article
- Article
- Dendritic cells from humans with hypomorphic mutations in IKBKG/NEMO have impaired mitogen-activated protein kinase activity.Human mutation · 2011Article
- The zinc finger domain of IKKγ (NEMO) protein in health and disease.Journal of cellular and molecular medicine · 2010Review
- NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain.The EMBO journal · 2009Article
- Impaired priming and activation of the neutrophil NADPH oxidase in patients with IRAK4 or NEMO deficiency.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Hypomorphic nuclear factor-kappaB essential modulator mutation database and reconstitution system identifies phenotypic and immunologic diversity.The Journal of allergy and clinical immunology · 2008Article
- A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-truncated protein and is associated with ectodermal dysplasia with immunodeficiency.Human mutation · 2008Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Ectodermal dysplasia with immune deficiency (EDI) is caused by alterations in NEMO (nuclear factor [NF]-kappaB essential modulator). Most genetic mutations are located in exon 10 and affect the C-terminal zinc finger domain. However, the biochemical mechanism by which they cause immune dysfunction remains undetermined. In this report, we investigated the effect of a cysteine-to-arginine mutation (C417R) found in the NEMO zinc finger domain on dendritic cell (DC) function. Following CD40 stimulation of DCs prepared from 2 unrelated patients with the NEMO C417R mutation, we found NEMO ubiquitination was absent, and this was associated with preserved RelA but absent c-Rel activity. As a consequence, CD40 stimulated EDI DCs failed to synthesize the c-Rel-dependent cytokine interleukin-12, had impaired up-regulation of costimulatory molecules, and failed to support allogeneic lymphocyte proliferation in vitro. In contrast, EDI DCs stimulated with the TLR4 ligand lipopolysaccharide (LPS) showed normal downstream NF-kappaB activity, DC maturation, and NEMO ubiquitination. These findings show for the first time how mutations in the zinc finger domain of NEMO can lead to pathway specific defects in NEMO ubiquitination and thus immune deficiency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.