ArticleCell death & disease2016
NEMO regulates a cell death switch in TNF signaling by inhibiting recruitment of RIPK3 to the cell death-inducing complex II.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- GADD45β inhibits RIPK3-mediated NF-κB activation by interfering with NEMO-RIPK1-RIPK3 interactions.Cell death discovery · 2025Article
- Therapeutic strategies for fragile X syndrome and implications for other gene-silencing disorders.Nature genetics · 2025Review
- Incontinentia pigmenti underlies thymic dysplasia, autoantibodies to type I IFNs, and viral diseases.The Journal of experimental medicine · 2024Article
- Dual regulation of NEMO by Nrf2 and miR-125a inhibits ferroptosis and protects liver from endoplasmic reticulum stress-induced injury.Theranostics · 2024Article
- Pathogenic insights from genetic causes of autoinflammatory inflammasomopathies and interferonopathies.The Journal of allergy and clinical immunology · 2022Review
- Human Genetic Diseases Linked to the Absence of NEMO: An Obligatory Somatic Mosaic Disorder in Male.International journal of molecular sciences · 2022Review
- Methods to Study the Effect of IKK Inhibition on TNF-Inducing Apoptosis and Necroptosis in Cultured Cells.Methods in molecular biology (Clifton, N.J.) · 2021Article
- NF-κB signaling induces inductive expression of the downstream molecules and IgD gene in the freshwater carp,3 Biotech · 2020Article
- Life, death, and autophagy in cancer: NF-κB turns up everywhere.Cell death & disease · 2020Review
- RIPK1 and death receptor signaling drive biliary damage and early liver tumorigenesis in mice with chronic hepatobiliary injury.Cell death and differentiation · 2019Article
- Article
- Placental Expression of NEMO Protein in Normal Pregnancy and Preeclampsia.Disease markers · 2019Article
- Pro-inflammatory cytokines activate hypoxia-inducible factor 3α via epigenetic changes in mesenchymal stromal/stem cells.Scientific reports · 2018Article
- The isoprenoid end product N6-isopentenyladenosine reduces inflammatory response through the inhibition of the NFκB and STAT3 pathways in cystic fibrosis cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2018Article
- Necroptosis in development and diseases.Genes & development · 2018Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Incontinentia Pigmenti (IP) is a rare X-linked disease characterized by early male lethality and multiple abnormalities in heterozygous females. IP is caused by NF-κB essential modulator (NEMO) mutations. The current mechanistic model suggests that NEMO functions as a crucial component mediating the recruitment of the IκB-kinase (IKK) complex to tumor necrosis factor receptor 1 (TNF-R1), thus allowing activation of the pro-survival NF-κB response. However, recent studies have suggested that gene activation and cell death inhibition are two independent activities of NEMO. Here we describe that cells expressing the IP-associated NEMO-A323P mutant had completely abrogated TNF-induced NF-κB activation, but retained partial antiapoptotic activity and exhibited high sensitivity to death by necroptosis. We found that robust caspase activation in NEMO-deficient cells is concomitant with RIPK3 recruitment to the apoptosis-mediating complex. In contrast, cells expressing the ubiquitin-binding mutant NEMO-A323P did not recruit RIPK3 to complex II, an event that prevented caspase activation. Hence NEMO, independently from NF-κB activation, represents per se a key component in the structural and functional dynamics of the different TNF-R1-induced complexes. Alteration of this process may result in differing cellular outcomes and, consequently, also pathological effects in IP patients with different NEMO mutations.
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