ArticleProceedings of the National Academy of Sciences of the United States of America2016
Recruitment of A20 by the C-terminal domain of NEMO suppresses NF-κB activation and autoinflammatory disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 70 citations in OpenAlex.
- The ubiquitin-editing enzyme A20 (TNFAIP3): mechanisms of activation, biological function, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells.Nature biotechnology · 2026Article
- BIRC3 (Encoding cIAP2) Variants Result in Dysregulated RIPK1 Signaling Leading to Increased Epithelial Cell Death and Are Associated With Monogenic Crohn's Disease.Gastroenterology · 2026Article
- From RIPK1 to Necroptosis: Pathogenic Mechanisms in Neurodegenerative Diseases.Neurochemical research · 2025Review
- Hyperinflammation and Blindness. Screening for ROSAH Syndrome.European journal of case reports in internal medicine · 2025Article
- A20 as a Potential Therapeutic Target for COVID-19.Immunity, inflammation and disease · 2025Review
- TBK1-associated adapters TANK and AZI2 protect mice against TNF-induced cell death and severe autoinflammatory diseases.Nature communications · 2024Article
- LUBAC enables tumor-promoting LTβ receptor signaling by activating canonical NF-κB.Cell death and differentiation · 2024Article
- A20 in Kidney Transplantation and Autoimmunity.International journal of molecular sciences · 2024Review
- DecipheringmSystems · 2024Article
- Case Report: Diagnosis and treatment ofFrontiers in pediatrics · 2024Article
- A case report of neonatal incontinentia pigmenti complicated by severe cerebrovascular lesions in one of the male monozygotic twins.Frontiers in pediatrics · 2024Article
- NEMO reshapes the α-Synuclein aggregate interface and acts as an autophagy adapter by co-condensation with p62.Nature communications · 2023Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- USP10 regulates macrophage inflammation responses via stabilizing NEMO in LPS-induced sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Death by TNF: a road to inflammation.Nature reviews. Immunology · 2023Review
- Mistuned NF-κB signaling in lymphocytes: lessons from relevant inborn errors of immunity.Clinical and experimental immunology · 2023Article
- Persistent Lipid Accumulation Leads to Persistent Exacerbation of Endoplasmic Reticulum Stress and Inflammation in Progressive NASH via the IRE1α/TRAF2 Complex.Molecules (Basel, Switzerland) · 2023Article
- Genetically programmed alternative splicing of NEMO mediates an autoinflammatory disease phenotype.The Journal of clinical investigation · 2022Article
- Paediatric Behçet's Disease: A Comprehensive Review with an Emphasis on Monogenic Mimics.Journal of clinical medicine · 2022Review
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Receptor-induced NF-κB activation is controlled by NEMO, the NF-κB essential modulator. Hypomorphic NEMO mutations result in X-linked ectodermal dysplasia with anhidrosis and immunodeficiency, also referred to as NEMO syndrome. Here we describe a distinct group of patients with NEMO C-terminal deletion (ΔCT-NEMO) mutations. Individuals harboring these mutations develop inflammatory skin and intestinal disease in addition to ectodermal dysplasia with anhidrosis and immunodeficiency. Both primary cells from these patients, as well as reconstituted cell lines with this deletion, exhibited increased IκB kinase (IKK) activity and production of proinflammatory cytokines. Unlike previously described loss-of-function mutations, ΔCT-NEMO mutants promoted increased NF-κB activation in response to TNF and Toll-like receptor stimulation. Investigation of the underlying mechanisms revealed impaired interactions with A20, a negative regulator of NF-κB activation, leading to prolonged accumulation of K63-ubiquitinated RIP within the TNFR1 signaling complex. Recruitment of A20 to the C-terminal domain of NEMO represents a novel mechanism limiting NF-κB activation by NEMO, and its absence results in autoinflammatory disease.
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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.