ArticleProceedings of the National Academy of Sciences of the United States of America2014
RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
201 citing papers in PubMed, 1 synthesis or guideline pooled it, 284 citations in OpenAlex.
- Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.Nature reviews. Drug discovery · 2020Pooled it
- Z-Nucleic Acid-Binding Protein (ZBP)1 (DAI/DLM1) Regulation in Antiviral Cell Death Pathways.Pathogens (Basel, Switzerland) · 2026Review
- The anti-tumour activity of TNF in melanoma is determined by cFLIP.Cell death & disease · 2026Article
- PANoptosis in the pathogenesis of myelodysplastic syndromes.Molecular oncology · 2026Review
- The dual role of RIPK family in IBD: from cell death to therapeutic targeting.Molecular medicine (Cambridge, Mass.) · 2026Review
- RIPK1 ubiquitination regulates its kinase-independent function in development and inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- The landscape of regulated cell death: It's all downhill from here.Molecular cell · 2026Review
- Targeting PANoptosis in atherosclerosis: bridging cell death mechanisms and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Proteasomal inhibition compromises microvascular integrity via distinct effects on non-immune endothelial cells and immune cells.Frontiers in immunology · 2026Article
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- RIPK1 autophosphorylation at S161 mediates cell death and inflammation.The Journal of experimental medicine · 2025Article
- Necroptotic cell death consequences and disease relevance.Nature immunology · 2025Review
- Insights on the crosstalk among different cell death mechanisms.Cell death discovery · 2025Review
- For Better or Worse: The Impact of Necrotic Cell Death Modalities.Advances in experimental medicine and biology · 2025Review
- Exploring the critical role of PANoptosis in the pathogenesis of intervertebral disc degeneration: mechanisms and potential therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- Development of a RIPK1 degrader to enhance antitumor immunity.Nature communications · 2024Article
- Estimating the Number of Polygenic Diseases Among Six Mutually Exclusive Entities of Non-Tumors and Cancer.International journal of molecular sciences · 2024Review
- Zinc finger domain of p62/SQSTM1 is involved in the necroptosis of human cisplatin‑resistant ovarian cancer cells treated with sulfasalazine.Oncology letters · 2024Article
- Blockade of IKK signaling induces RIPK1-independent apoptosis in human macrophages.PLoS pathogens · 2024Article
141 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
The pronecrotic kinase, receptor interacting protein (RIP1, also called RIPK1) mediates programmed necrosis and, together with its partner, RIP3 (RIPK3), drives midgestational death of caspase 8 (Casp8)-deficient embryos. RIP1 controls a second vital step in mammalian development immediately after birth, the mechanism of which remains unresolved. Rip1(-/-) mice display perinatal lethality, accompanied by gross immune system abnormalities. Here we show that RIP1 K45A (kinase dead) knockin mice develop normally into adulthood, indicating that development does not require RIP1 kinase activity. In the face of complete RIP1 deficiency, cells develop sensitivity to RIP3-mixed lineage kinase domain-like-mediated necroptosis as well as to Casp8-mediated apoptosis activated by diverse innate immune stimuli (e.g., TNF, IFN, double-stranded RNA). When either RIP3 or Casp8 is disrupted in combination with RIP1, the resulting double knockout mice exhibit slightly prolonged survival over RIP1-deficient animals. Surprisingly, triple knockout mice with combined RIP1, RIP3, and Casp8 deficiency develop into viable and fertile adults, with the capacity to produce normal levels of myeloid and lymphoid lineage cells. Despite the combined deficiency, these mice sustain a functional immune system that responds robustly to viral challenge. A single allele of Rip3 is tolerated in Rip1(-/-)Casp8(-/-)Rip3(+/-) mice, contrasting the need to eliminate both alleles of either Rip1 or Rip3 to rescue midgestational death of Casp8-deficient mice. These observations reveal a vital kinase-independent role for RIP1 in preventing pronecrotic as well as proapoptotic signaling events associated with life-threatening innate immune activation at the time of mammalian parturition.
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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.