ArticleCell death and differentiation2011
cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production.
Article in Cell death and differentiation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 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
200 citing papers in PubMed, 334 citations in OpenAlex.
- HERC4-mediated ubiquitination licenses RIPK1 to initiate TNF-induced cell death.Nature structural & molecular biology · 2026Article
- Cell death and its interaction with mitochondrial dysfunction in pathogenesis of acute pancreatitis: a comprehensive review.Apoptosis : an international journal on programmed cell death · 2026Review
- Procyanidin Capsules Combat ALF by Restoring Mitochondrial Homeostasis and Inhibiting Necroptosis via the PGAM5/DRP1/PINK1 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bidirectional Crosstalk Between cGAS-STING and Necroptosis: From Mitochondrial DNA Release to Inflammatory Disease.Drug design, development and therapy · 2026Review
- RIPK1 inhibition reduces biliary injury and fibrosis in primary sclerosing cholangitis.Science advances · 2025Article
- Review
- Integrated transcriptomics and metabolomics confirms the oxidative stress mechanism of hypothermia-induced neuronal necroptosis.Cellular & molecular biology letters · 2025Article
- Bypassing the guardian: regulated cell death pathways in p53-mutant cancers.Cellular & molecular biology letters · 2025Review
- PANoptosis: a potential target of atherosclerotic cardiovascular disease.Apoptosis : an international journal on programmed cell death · 2025Review
- Caffeic Acid Phenethyl Ester Protects Against Doxorubicin-Induced Cardiotoxicity via Inhibiting the ROS-MLKL-Mediated Cross-Talk Between Oxidative Stress and Necroptosis.Biomolecules · 2025Article
- Understanding TAK1 deficiency in microglia: Dual mechanisms for photoreceptor protection in a mouse model of retinitis pigmentosa.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Identification and Verification of Necroptosis-Related Genes in Patients With Sepsis by Bioinformatic Analysis and Molecular Experiments.Journal of cellular and molecular medicine · 2025Article
- Necroptosis in obesity: a complex cell death event.Apoptosis : an international journal on programmed cell death · 2025Review
- Airway remodeling in chronic obstructive pulmonary disease: characteristics and opportunities.Frontiers in medicine · 2025Review
- The role of reactive oxygen species in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection-induced cell death.Cellular & molecular biology letters · 2024Review
- Significance of Necroptosis in Cartilage Degeneration.Biomolecules · 2024Review
- Ferroptosis in health and disease.Redox biology · 2024Review
- Therapy-induced senescence through the redox lens.Redox biology · 2024Review
- Regulated cell death in hypoxic-ischaemic encephalopathy: recent development and mechanistic overview.Cell death discovery · 2024Review
- Research progress on morphology and mechanism of programmed cell death.Cell death & disease · 2024Review
140 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Three members of the IAP family (X-linked inhibitor of apoptosis (XIAP), cellular inhibitor of apoptosis proteins-1/-2 (cIAP1 and cIAP2)) are potent suppressors of apoptosis. Recent studies have shown that cIAP1 and cIAP2, unlike XIAP, are not direct caspase inhibitors, but block apoptosis by functioning as E3 ligases for effector caspases and receptor-interacting protein 1 (RIP1). cIAP-mediated polyubiquitination of RIP1 allows it to bind to the pro-survival kinase transforming growth factor-β-activated kinase 1 (TAK1) which prevents it from activating caspase-8-dependent death, a process reverted by the de-ubiquitinase CYLD. RIP1 is also a regulator of necrosis, a caspase-independent type of cell death. Here, we show that cells depleted of the IAPs by treatment with the IAP antagonist BV6 are greatly sensitized to tumor necrosis factor (TNF)-induced necrosis, but not to necrotic death induced by anti-Fas, poly(I:C) oxidative stress. Specific targeting of the IAPs by RNAi revealed that repression of cIAP1 is responsible for the sensitization. Similarly, lowering TAK1 levels or inhibiting its kinase activity sensitized cells to TNF-induced necrosis, whereas repressing CYLD had the opposite effect. We show that this sensitization to death is accompanied by enhanced RIP1 kinase activity, increased recruitment of RIP1 to Fas-associated via death domain and RIP3 (which allows necrosome formation), and elevated RIP1 kinase-dependent accumulation of reactive oxygen species (ROS). In conclusion, our data indicate that cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent ROS production.
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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.