ArticleNature2014
RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
197 citing papers in PubMed, 316 citations in OpenAlex.
- Early Development of Ocadusertib, a Selective Receptor-Interacting Serine/Threonine-Protein Kinase 1 Inhibitor.Clinical and translational science · 2026Trial
- The dual role of RIPK family in IBD: from cell death to therapeutic targeting.Molecular medicine (Cambridge, Mass.) · 2026Review
- Arginine Di-methylation of RIP3 safeguards necroptosis for intestinal homeostasis.Cell death and differentiation · 2026Article
- Ripk1 is critical for preserving effector regulatory T cells and the suppressive transcriptional program in regulatory T cells.Cell death and differentiation · 2026Article
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- Gastroenterological disorders in inborn errors of immunity. Part 2 A. Overview of selected diseases.Przeglad gastroenterologiczny · 2026Review
- Recent advances in targeting protein degradation for tumor immunotherapy.Journal of hematology & oncology · 2025Review
- RIPK1 autophosphorylation at S161 mediates cell death and inflammation.The Journal of experimental medicine · 2025Article
- Inhibition of TBK1/IKKε mediated RIPK1 phosphorylation sensitizes tumors to immune cell killing.Cell death discovery · 2025Article
- Regulation of inflammatory processes by caspases.Nature reviews. Molecular cell biology · 2025Review
- RIPK1 kinase drove brain microvascular endothelial cells death and blood-brain barrier disruption in neonatal Escherichia coli meningitis.Nature communications · 2025Article
- Development of Potent and Selective RIPK1 Degraders Targeting Its Nonenzymatic Function for Cancer Treatment.Journal of medicinal chemistry · 2025Article
- Reduction of intestinal RIPK1 ameliorates HFD-induced metabolic disorders in female mice.iScience · 2025Article
- 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
- Review
- RIPK1 signaling pathways: implications for autoimmune and neuroinflammatory diseases.Frontiers in immunology · 2025Review
- Paneth cell TNF signaling induces gut bacterial translocation and sepsis.Cell host & microbe · 2024Article
- Article
- METTL3 restricts RIPK1-dependent cell death via the ATF3-cFLIP axis in the intestinal epithelium.Cell regeneration (London, England) · 2024Article
137 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Receptor interacting protein kinase 1 (RIPK1) has an essential role in the signalling triggered by death receptors and pattern recognition receptors. RIPK1 is believed to function as a node driving NF-κB-mediated cell survival and inflammation as well as caspase-8 (CASP8)-dependent apoptotic or RIPK3/MLKL-dependent necroptotic cell death. The physiological relevance of this dual function has remained elusive because of the perinatal death of RIPK1 full knockout mice. To circumvent this problem, we generated RIPK1 conditional knockout mice, and show that mice lacking RIPK1 in intestinal epithelial cells (IECs) spontaneously develop severe intestinal inflammation associated with IEC apoptosis leading to early death. This early lethality was rescued by antibiotic treatment, MYD88 deficiency or tumour-necrosis factor (TNF) receptor 1 deficiency, demonstrating the importance of commensal bacteria and TNF in the IEC Ripk1 knockout phenotype. CASP8 deficiency, but not RIPK3 deficiency, rescued the inflammatory phenotype completely, indicating the indispensable role of RIPK1 in suppressing CASP8-dependent apoptosis but not RIPK3-dependent necroptosis in the intestine. RIPK1 kinase-dead knock-in mice did not exhibit any sign of inflammation, suggesting that RIPK1-mediated protection resides in its kinase-independent platform function. Depletion of RIPK1 in intestinal organoid cultures sensitized them to TNF-induced apoptosis, confirming the in vivo observations. Unexpectedly, TNF-mediated NF-κB activation remained intact in these organoids. Our results demonstrate that RIPK1 is essential for survival of IECs, ensuring epithelial homeostasis by protecting the epithelium from CASP8-mediated IEC apoptosis independently of its kinase activity and NF-κB activation.
Indexed as
Identifiers
What OpenQuestion holds
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.