ArticleBlood2011
New mechanism of X-linked anhidrotic ectodermal dysplasia with immunodeficiency: impairment of ubiquitin binding despite normal folding of NEMO protein.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 57 citations in OpenAlex.
- Pediatric ectodermal dysplasia with immunodeficiency caused by a hemizygousFrontiers in immunology · 2026Review
- Review
- NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62.Nature communications · 2023Article
- Skin manifestations of inborn errors of NF-κB.Frontiers in pediatrics · 2022Review
- Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study.Signal transduction and targeted therapy · 2020Review
- Linear Ubiquitin Code: Its Writer, Erasers, Decoders, Inhibitors, and Implications in Disorders.International journal of molecular sciences · 2020Review
- Article
- Lessons learned from the study of human inborn errors of innate immunity.The Journal of allergy and clinical immunology · 2019Review
- Rescue of recurrent deep intronic mutation underlying cell type-dependent quantitative NEMO deficiency.The Journal of clinical investigation · 2019Article
- The role of hybrid ubiquitin chains in the MyD88 and other innate immune signalling pathways.Cell death and differentiation · 2017Review
- The PP4R1 sub-unit of protein phosphatase PP4 is essential for inhibition of NF-κB by merkel polyomavirus small tumour antigen.Oncotarget · 2017Article
- Review
- Ubiquitin signaling in immune responses.Cell research · 2016Review
- Recruitment of A20 by the C-terminal domain of NEMO suppresses NF-κB activation and autoinflammatory disease.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Inhibition of Canonical NF-κB Signaling by a Small Molecule Targeting NEMO-Ubiquitin Interaction.Scientific reports · 2016Article
- Linear ubiquitination in immunity.Immunological reviews · 2015Review
- Linear ubiquitination signals in adaptive immune responses.Immunological reviews · 2015Review
- Rare mendelian primary immunodeficiency diseases associated with impaired NF-κB signaling.Genes and immunity · 2015Review
- Inherited and acquired immunodeficiencies underlying tuberculosis in childhood.Immunological reviews · 2015Review
- Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity.Seminars in immunology · 2014Review
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 4 countries.
Funding
Abstract
Nuclear factor-κB essential modulator (NEMO), the regulatory subunit of the IκB kinase complex, is a critical component of the NF-κB pathway. Hypomorphic mutations in the X-linked human NEMO gene cause various forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID). All known X-linked EDA-ID-causing mutations impair NEMO protein expression, folding, or both. We describe here 2 EDA-ID-causing missense mutations that affect the same residue in the CC2-LZ domain (D311N and D311G) that do not impair NEMO production or folding. Structural studies based on pull-down experiments showed a defect in noncovalent interaction with K63-linked and linear polyubiquitin chains for these mutant proteins. Functional studies on the patients' cells showed an impairment of the classic NF-κB signaling pathways after activation of 2 NEMO ubiquitin-binding-dependent receptors, the TNF and IL-1β receptors, and in the CD40-dependent NF-κB pathway. We report the first human NEMO mutations responsible for X-linked EDA-ID found to affect the polyubiquitin binding of NEMO rather than its expression and folding. These experiments demonstrate that the binding of human NEMO to polyubiquitin is essential for NF-κB activation. They also demonstrate that the normal expression and folding of NEMO do not exclude a pathogenic role for NEMO mutations in patients with EDA-ID.
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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.