ArticleCell death and differentiation2009
NEMO/IKKgamma regulates an early NF-kappaB-independent cell-death checkpoint during TNF signaling.
Article in Cell death and differentiation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
60 citing papers in PubMed, 109 citations in OpenAlex.
- Loss of the kinases TBK1 and IKKε sensitizes target cancer cells to T cell killing through an IFN-γ-mediated inflammatory death program.Science signaling · 2026Article
- Mendelian susceptibility to mycobacterial disease: IFN-γ-driven immunity collapse underlies heterogeneous infections.Frontiers in immunology · 2026Review
- The Anti-Oxidative, Anti-Inflammatory, Anti-Apoptotic, and Anti-Necroptotic Role of Zinc in COVID-19 and Sepsis.Antioxidants (Basel, Switzerland) · 2023Review
- The therapeutic potential of targeting regulated non-apoptotic cell death.Nature reviews. Drug discovery · 2023Review
- LncRNA Gm26917 regulates inflammatory response in macrophages by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury.Frontiers in pharmacology · 2022Article
- Necroptosis: A new target for prevention of osteoporosis.Frontiers in endocrinology · 2022Review
- Non-coding RNAs in necroptosis, pyroptosis, and ferroptosis in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Review
- Article
- Protein Kinase-Mediated Decision Between the Life and Death.Advances in experimental medicine and biology · 2021Article
- The Critical Role of PARPs in Regulating Innate Immune Responses.Frontiers in immunology · 2021Review
- 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
- Current translational potential and underlying molecular mechanisms of necroptosis.Cell death & disease · 2019Review
- The many faces of tumor necrosis factor signaling in the intestinal epithelium.Genes and immunity · 2019Review
- Article
- Keeping Cell Death in Check: Ubiquitylation-Dependent Control of TNFR1 and TLR Signaling.Frontiers in cell and developmental biology · 2019Article
- Ripoptocide - A Spark for Inflammation.Frontiers in cell and developmental biology · 2019Review
- Dysregulation of Intestinal Epithelial Cell RIPK Pathways Promotes Chronic Inflammation in the IBD Gut.Frontiers in immunology · 2019Review
- Placental Expression of NEMO Protein in Normal Pregnancy and Preeclampsia.Disease markers · 2019Article
- Bypassing drug resistance by triggering necroptosis: recent advances in mechanisms and its therapeutic exploitation in leukemia.Journal of experimental & clinical cancer research : CR · 2018Review
- TBK1 and IKKε prevent TNF-induced cell death by RIPK1 phosphorylation.Nature cell biology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
TNF receptor 1 (TNFR1) ligation can result in cell survival or cell death. What determines which of the two opposing responses is triggered is not fully understood. The current model suggests that it is the activation of the NF-kappaB pathway and its induction of prosurvival genes, or the lack thereof, which determines the outcome. NF-kappaB essential modifier (NEMO)/IkappaB kinase-gamma (IKKgamma)-deficient cells are highly sensitive to apoptosis, and as NEMO is essential for NF-kappaB activation, it has been assumed that this is due to the lack of NF-kappaB. This study demonstrates that this assumption was incorrect and that NEMO has another antiapoptotic function that is independent of its role in the NF-kappaB pathway. NEMO prevents receptor interacting protein-1 (RIP1) from engaging CASPASE-8 before NF-kappaB-mediated induction of antiapoptotic genes. Without NEMO, RIP1 associates with CASPASE-8 resulting in rapid tumor necrosis factor (TNF)-induced apoptosis. These results suggest that there are two cell-death checkpoints following TNF stimulation: an early transcription-independent checkpoint whereby NEMO restrains RIP1 from activating the caspase cascade, followed by a later checkpoint dependent on NF-kappaB-mediated transcription of prosurvival genes.
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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.