ArticleScience (New York, N.Y.)2014
Activity of protein kinase RIPK3 determines whether cells die by necroptosis or apoptosis.
Article in Science (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 439 papers.
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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.
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Who cites it
439 citing papers in PubMed, 672 citations in OpenAlex.
- Early Development of Ocadusertib, a Selective Receptor-Interacting Serine/Threonine-Protein Kinase 1 Inhibitor.Clinical and translational science · 2026Trial
- Ischemia-Reperfusion Injury in Free Flaps: Molecular Mechanisms and Protective Effects of Remote Ischemic Preconditioning.Journal of cellular and molecular medicine · 2025Trial
- A phase I, randomized, ascending-dose study to assess safety, pharmacokinetics, and activity of GDC-8264, a RIP1 inhibitor, in healthy volunteers.Clinical and translational science · 2023Trial
- Harnessing necroptosis via RIPK1 degradation to potentiate radio-immunotherapy in cervical cancer.Bioactive materials · 2027Article
- HERC4-mediated ubiquitination licenses RIPK1 to initiate TNF-induced cell death.Nature structural & molecular biology · 2026Article
- Radiotherapy-Induced Side Effects: Epidemiology, Pathogenesis, Prevention and Treatments.MedComm · 2026Review
- RIPK3 acts as a molecular switch between neuroprotection and neuropathology during herpes simplex encephalitis.Nature communications · 2026Article
- Remote intestinal changes following blast-induced thoracic trauma with transient hemorrhagic shock and hind-limb ischemia.Intensive care medicine experimental · 2026Article
- 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
- The kinase domain of RIPK3 tunes its scaffolding functions.Cell death and differentiation · 2026Article
- Black Sheep: Pseudokinases Bucking the Trend to Reveal Non-Catalytic Kinase Functions.IUBMB life · 2026Review
- Review
- GSK'872 mitigates ischemia-reperfusion injury in rat lung transplants by regulating PANoptosis and inflammation in cell type specific manner.Cell communication and signaling : CCS · 2026Article
- A chemo-free thermo-sensitive necroptosis-inducing perfusate to enable potent hyperthermic intraperitoneal immunotherapy.National science review · 2026Article
- Redirecting TRIM21 with TRIMTACs for the targeted degradation of multimeric proteins.The FEBS journal · 2026Review
- Adipocyte caspase-8 but not RIPK3 promotes adiposity.Cell death discovery · 2026Article
- Oncogenic KRAS-driven type I interferon signalling primes pancreatic cancer for necroptosis.Nature communications · 2026Article
- 6-Shogaol Attenuates Doxorubicin-Induced Cardiac and Skeletal Muscle Atrophy by Inhibiting E3 Ubiquitin Ligases and Necroptosis.Phytotherapy research : PTR · 2026Article
- [Fecal microbiota transplantation attenuates gastrointestinal inflammation in murine acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation by inhibiting RIPK1/RIPK3-mediated necroptosis].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026Article
379 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 trigger pro-inflammatory cell death termed "necroptosis." Studies with RIPK3-deficient mice or the RIPK1 inhibitor necrostatin-1 suggest that necroptosis exacerbates pathology in many disease models. We engineered mice expressing catalytically inactive RIPK3 D161N or RIPK1 D138N to determine the need for the active kinase in the whole animal. Unexpectedly, RIPK3 D161N promoted lethal RIPK1- and caspase-8-dependent apoptosis. In contrast, mice expressing RIPK1 D138N were viable and, like RIPK3-deficient mice, resistant to tumor necrosis factor (TNF)-induced hypothermia. Cells expressing RIPK1 D138N were resistant to TNF-induced necroptosis, whereas TNF-induced signaling pathways promoting gene transcription were unperturbed. Our data indicate that the kinase activity of RIPK3 is essential for necroptosis but also governs whether a cell activates caspase-8 and dies by apoptosis.
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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.