ArticleCell death & disease2013
TNF can activate RIPK3 and cause programmed necrosis in the absence of RIPK1.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 152 citations in OpenAlex.
- Ischemia-Reperfusion Injury in Free Flaps: Molecular Mechanisms and Protective Effects of Remote Ischemic Preconditioning.Journal of cellular and molecular medicine · 2025Trial
- Necroptotic cell death and immunomodulator release induced by T-cell engaging anti-lymphoma therapies.Cell death & disease · 2026Article
- Bacterial reporter-paired scRNA sequencing reveals cross talk between zinc starvation and zinc toxicity in macrophage antibacterial defense.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Human cytomegalovirus-triggered necroptosis is suppressed by sequestration of MLKL in the nucleus of infected monocytes.Journal of virology · 2025Article
- Histone deacetylase 7 mediates lipopolysaccharide-inducible mitochondrial fission in macrophages.Journal of cell science · 2025Article
- Neutrophils and NETs in Pathophysiology and Treatment of Inflammatory Bowel Disease.International journal of molecular sciences · 2025Review
- Harnessing the FGFR2/NF2/YAP signaling-dependent necroptosis to develop an FGFR2/IL-8 dual blockade therapeutic strategy.Nature communications · 2025Article
- TBK1 and IKKε prevent premature cell death by limiting the activity of both RIPK1 and NLRP3 death pathways.Science advances · 2025Article
- Insights on the crosstalk among different cell death mechanisms.Cell death discovery · 2025Review
- Divergent roles of RIPK3 and MLKL in high-fat diet-induced obesity and MAFLD in mice.Life science alliance · 2025Article
- The research potential of A20 in psoriatic arthritis.Frontiers in immunology · 2025Review
- Unveiling the hidden dangers: a review of non-apoptotic programmed cell death in anesthetic-induced developmental neurotoxicity.Cell biology and toxicology · 2024Review
- A RIPK1-specific PROTAC degrader achieves potent antitumor activity by enhancing immunogenic cell death.Immunity · 2024Article
- Cellular heterogeneity in TNF/TNFR1 signalling: live cell imaging of cell fate decisions in single cells.Cell death & disease · 2024Review
- cIAPs control RIPK1 kinase activity-dependent and -independent cell death and tissue inflammation.The EMBO journal · 2023Article
- The effect of hyperthyroidism on cognitive function, neuroinflammation, and necroptosis in APP/PS1 mice.Journal of translational medicine · 2023Article
- The host-directed therapeutic imatinib mesylate accelerates immune responses to Mycobacterium marinum infection and limits pathology associated with granulomas.PLoS pathogens · 2023Article
- An in vitro evaluation of the antioxidant activities of necroptosis and apoptosis inhibitors: the potential of necrostatin-1 and necrostatin-1i to have radical scavenging activities.Pharmacological reports : PR · 2023Article
- The Interplay Between Autophagy and Regulated Necrosis.Antioxidants & redox signaling · 2023Review
- Curcumin alleviates experimental colitis in mice by suppressing necroptosis of intestinal epithelial cells.Frontiers in pharmacology · 2023Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ligation of tumor necrosis factor receptor 1 (TNFR1) can cause cell death by caspase 8 or receptor-interacting protein kinase 1 (RIPK1)- and RIPK3-dependent mechanisms. It has been assumed that because RIPK1 bears a death domain (DD), but RIPK3 does not, RIPK1 is necessary for recruitment of RIPK3 into signaling and death-inducing complexes. To test this assumption, we expressed elevated levels of RIPK3 in murine embryonic fibroblasts (MEFs) from wild-type (WT) and gene-deleted mice, and exposed them to TNF. Neither treatment with TNF nor overexpression of RIPK3 alone caused MEFs to die, but when levels of RIPK3 were increased, addition of TNF killed WT, Ripk1(-/-), caspase 8(-/-), and Bax(-/-)/Bak(-/-) MEFs, even in the presence of the broad-spectrum caspase inhibitor Q-VD-OPh. In contrast, Tnfr1(-/-) and Tradd(-/-) MEFs did not die. These results show for the first time that in the absence of RIPK1, TNF can activate RIPK3 to induce cell death both by a caspase 8-dependent mechanism and by a separate Bax/Bak- and caspase-independent mechanism. RIPK1 is therefore not essential for TNF to activate RIPK3 to induce necroptosis nor for the formation of a functional ripoptosome/necrosome.
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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.