ArticleNature2011
Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 801 papers, 3 of them syntheses that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
801 citing papers in PubMed, 3 syntheses or guidelines pooled it, 1,242 citations in OpenAlex.
- Necroptosis as a key player in cervical cancer progression and management: a systematic review and transcriptomic cross-study consensus analysis.Apoptosis : an international journal on programmed cell death · 2026Pooled it
- TNFα-Related Chondrocyte Inflammation Models: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- The romantic history of signaling pathway discovery in cell death: an updated review.Molecular and cellular biochemistry · 2024Pooled it
- Metabolic hallmarks of regulated cell death.Cell research · 2026Review
- A Novel Biofilm Amyloid Ligand for Caspase-11 Drives Hyperactivation in Dendritic Cells.bioRxiv : the preprint server for biology · 2026Article
- The NLRP3 inflammasome at the crossroads of innate immune signaling and cell death.Cellular & molecular immunology · 2026Review
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Z-Nucleic Acid-Binding Protein (ZBP)1 (DAI/DLM1) Regulation in Antiviral Cell Death Pathways.Pathogens (Basel, Switzerland) · 2026Review
- Birinapant enhances cisplatin sensitivity in epithelial ovarian cancer through modulation of apoptotic and survival signaling pathways.Cancer chemotherapy and pharmacology · 2026Article
- Role of PANoptosis in the development of gastric immunity and related gastric mucosal disease (Review).Molecular medicine reports · 2026Review
- cFLIP suppresses caspase-1- and MLKL-independent perinatal lethality driven by auto-processing impaired caspase-8 D387A.Cell death and differentiation · 2026Article
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Cooperation and constraint: the complex association of caspase-8 and cFLIP.Cell death and differentiation · 2026Article
- Neuroinflammation and Graft Survival in Pluripotent Stem Cell-Derived Therapies for the Central Nervous System.Journal of neurochemistry · 2026Review
- Sublethal Caspase-8 Activation Drives Radiation-Induced Genetic Instability and Oncogenic Transformation Through Endonuclease G and Non-Canonical NF-κB Signaling.International journal of molecular sciences · 2026Article
- The kinase domain of RIPK3 tunes its scaffolding functions.Cell death and differentiation · 2026Article
- Review
- NAD+ depletion links metabolic stress to drive innate immune priming and selectively control PANoptosis.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Regulated cell death plasticity in cancer: thresholds, reversibility, and therapeutic failure.Journal of translational medicine · 2026Review
- Molecular switches in cell death: the interplay of apoptosis and pyroptosis in cancer.Cell communication and signaling : CCS · 2026Review
741 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Caspase-8 has two opposing biological functions--it promotes cell death by triggering the extrinsic pathway of apoptosis, but also has a survival activity, as it is required for embryonic development, T-lymphocyte activation, and resistance to necrosis induced by tumour necrosis factor-α (TNF-α) and related family ligands. Here we show that development of caspase-8-deficient mice is completely rescued by ablation of receptor interacting protein kinase-3 (RIPK3). Adult animals lacking both caspase-8 and RIPK3 display a progressive lymphoaccumulative disease resembling that seen with defects in CD95 or CD95-ligand (also known as FAS and FASLG, respectively), and resist the lethal effects of CD95 ligation in vivo. We have found that caspase-8 prevents RIPK3-dependent necrosis without inducing apoptosis by functioning in a proteolytically active complex with FLICE-like inhibitory protein long (FLIP(L), also known as CFLAR), and this complex is required for the protective function.
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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.