ArticleProceedings of the National Academy of Sciences of the United States of America2013
Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 221 papers, 1 of them a synthesis that pooled it.
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Who cites it
221 citing papers in PubMed, 1 synthesis or guideline pooled it, 345 citations in OpenAlex.
- Necroptosis in pancreatic cancer: Molecular mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2026Pooled it
- Matrix Metalloproteinase-8 Deficiency Alters the Balance Between Viral Clearance and Immunopathology in H1N1 Infection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- PANoptosis in the pathogenesis of myelodysplastic syndromes.Molecular oncology · 2026Review
- Review
- The Tumor-Promoting Role of ADM in Bladder Cancer and its Mediated Mechanisms of Cell Death via PKR and STAT1.Applied biochemistry and biotechnology · 2026Article
- ISG15 negatively regulates RIPK3-mediated cell death and viral pathogenesis.Cell reports · 2026Article
- Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics.Apoptosis : an international journal on programmed cell death · 2026Review
- The critical role of necroptosis in oil cyst formation associated with autologous fat transplantation.Cell communication and signaling : CCS · 2026Article
- Artemisinin attenuates 3-nitropropionic acid-induced neurodegeneration via HMGB1/TLR4/NF-κB modulation in a rat model of huntington's disease.Archives of pharmacal research · 2026Article
- Targeting MLKL-Driven Necroptosis: A Therapeutic Target in Inflammation and Host Defense.Biomolecules · 2026Review
- RIPK1 regulates β-cell fate via actions on gene expression and kinase signaling in a mouse model of β-cell self-reactivity.Cell death & disease · 2026Article
- Host- and genotype-specific transcriptomic responses toFrontiers in immunology · 2026Article
- GADD45β inhibits RIPK3-mediated NF-κB activation by interfering with NEMO-RIPK1-RIPK3 interactions.Cell death discovery · 2025Article
- Trigger Points of Necroptosis (RIPK1, RIPK3, and MLKL)-Promising Horizon or Blind Alley in Therapy of Colorectal Cancer?International journal of molecular sciences · 2025Review
- Advances inMicroorganisms · 2025Review
- Early and opposing neutrophil and CD4 T cell responses shape pulmonary tuberculosis pathology.The Journal of experimental medicine · 2025Article
- The Interplay Between Therapeutic Self-Amplifying RNA and the Innate Immune System: Balancing Efficiency and Reactogenicity.International journal of molecular sciences · 2025Review
- Reprogramming RIPK3-induced cell death in malignant B cells promotes immune-mediated tumor control.Science advances · 2025Article
- Mitigating Effect of Ginger Extract on Survival Rate and Muscle Quality of Crucian Carp (International journal of molecular sciences · 2025Article
161 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Interferons (IFNs) are cytokines with powerful immunomodulatory and antiviral properties, but less is known about how they induce cell death. Here, we show that both type I (α/β) and type II (γ) IFNs induce precipitous receptor-interacting protein (RIP)1/RIP3 kinase-mediated necrosis when the adaptor protein Fas-associated death domain (FADD) is lost or disabled by phosphorylation, or when caspases (e.g., caspase 8) are inactivated. IFN-induced necrosis proceeds via progressive assembly of a RIP1-RIP3 "necrosome" complex that requires Jak1/STAT1-dependent transcription, but does not need the kinase activity of RIP1. Instead, IFNs transcriptionally activate the RNA-responsive protein kinase PKR, which then interacts with RIP1 to initiate necrosome formation and trigger necrosis. Although IFNs are powerful activators of necrosis when FADD is absent, these cytokines are likely not the dominant inducers of RIP kinase-driven embryonic lethality in FADD-deficient mice. We also identify phosphorylation on serine 191 as a mechanism that disables FADD and collaborates with caspase inactivation to allow IFN-activated necrosis. Collectively, these findings outline a mechanism of IFN-induced RIP kinase-dependent necrotic cell death and identify FADD and caspases as negative regulators of this process.
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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.