ArticlePLoS biology2021
A unique death pathway keeps RIPK1 D325A mutant mice in check at embryonic day 10.5.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 27 citations in OpenAlex.
- Caspase-8 silences cell death-independent constitutive immune activation driven by tonic TNF-α.EMBO reports · 2026Article
- Tau aggregates cause reactivation of transposable DNA elements, leading to Z-RNA-ZBP1-mediated neuronal death.Nature neuroscience · 2026Article
- 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
- ADAR1 as a Placental Innate Immune Rheostat Sustaining the Homeostatic Balance of Intrinsic Interferon Response at the Maternal-Fetal Interface.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Three decades of caspases and RIPKs in life and death.Human molecular genetics · 2025Review
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- Influenza virus infection activates TAK1 to suppress RIPK3-independent apoptosis and RIPK1-dependent necroptosis.Cell communication and signaling : CCS · 2024Article
- The interaction between RIPK1 and FADD controls perinatal lethality and inflammation.Cell reports · 2024Article
- Phosphorylation of caspase-8 by RSKs via organ-constrained effects controls the sensitivity to TNF-induced death.Cell death discovery · 2024Article
- RIPK3 cleavage is dispensable for necroptosis inhibition but restricts NLRP3 inflammasome activation.Cell death and differentiation · 2024Article
- Cytokine Profile in Predicting the Effectiveness of Advanced Therapy for Ulcerative Colitis: A Narrative Review.Biomedicines · 2024Review
- Anthrax lethal toxin and tumor necrosis factor-α synergize on intestinal epithelia to induce mouse death.Protein & cell · 2024Article
- Targeting RIPK1 kinase for modulating inflammation in human diseases.Frontiers in immunology · 2023Review
- TNF-dependent hyperactivation of RIPK1-dependent cytotoxic signaling during embryogenesis and inflammation.PLoS biology · 2021Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor receptor-1 (TNFR1) signaling, apart from its pleiotropic functions in inflammation, plays a role in embryogenesis as deficiency of varieties of its downstream molecules leads to embryonic lethality in mice. Caspase-8 noncleavable receptor interacting serine/threonine kinase 1 (RIPK1) mutations occur naturally in humans, and the corresponding D325A mutation in murine RIPK1 leads to death at early midgestation. It is known that both the demise of Ripk1D325A/D325A embryos and the death of Casp8-/- mice are initiated by TNFR1, but they are mediated by apoptosis and necroptosis, respectively. Here, we show that the defects in Ripk1D325A/D325A embryos occur at embryonic day 10.5 (E10.5), earlier than that caused by Casp8 knockout. By analyzing a series of genetically mutated mice, we elucidated a mechanism that leads to the lethality of Ripk1D325A/D325A embryos and compared it with that underlies Casp8 deletion-mediated lethality. We revealed that the apoptosis in Ripk1D325A/D325A embryos requires a scaffold function of RIPK3 and enzymatically active caspase-8. Unexpectedly, caspase-1 and caspase-11 are downstream of activated caspase-8, and concurrent depletion of Casp1 and Casp11 postpones the E10.5 lethality to embryonic day 13.5 (E13.5). Moreover, caspase-3 is an executioner of apoptosis at E10.5 in Ripk1D325A/D325A mice as its deletion extends life of Ripk1D325A/D325A mice to embryonic day 11.5 (E11.5). Hence, an unexpected death pathway of TNFR1 controls RIPK1 D325A mutation-induced lethality at E10.5.
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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.