ArticleNature communications2024
Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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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
19 citing papers in PubMed.
- Death domain-mediated higher-order oligomerization of RIPK1 drives TNF-induced signaling.Cell death and differentiation · 2026Article
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Multi-omics and experimental evidence in human chondrocytes identify caspase-8 as a non-apoptotic regulator of inflammatory, senescent, and fibrotic signaling in osteoarthritis.Cell communication and signaling : CCS · 2026Article
- Recombinant Dabie bandavirus as a bivalent vaccine platform inducing protective immunity against intracellular pathogens and cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Decoding necrosome assembly: harmonizing signal amplification and attenuation through optimal RIP3 stoichiometry.Nature communications · 2025Article
- Review
- Article
- Cryo-EM reveals molecular mechanisms underlying the inhibitory effect of netrin-4 on laminin matrix formation.Nature communications · 2025Article
- Assembly and activation of the death-inducing signaling complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nuclear respiratory factor-1 promotes CFLAR transcription in H9C2 cardiomyocytes, protecting them against hypoxia-induced apoptosis.Molecular biology reports · 2025Article
- FLIPProceedings of the National Academy of Sciences of the United States of America · 2025Article
- A structural atlas of death domain fold proteins reveals their versatile roles in biology and function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions.Antioxidants (Basel, Switzerland) · 2025Review
- Impaired NLRP3 inflammasome signaling diverts pyroptotic to apoptotic caspase activation in macrophages.Frontiers in immunology · 2025Article
- Pharmacological mechanisms and therapeutic prospects of plant metabolites from traditional Chinese medicine in regulating programmed cell death in Alzheimer's disease.Frontiers in pharmacology · 2025Review
- Review
- Reverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes.Nature communications · 2024Article
- Interactions between tumor-associated macrophages and regulated cell death: therapeutic implications in immuno-oncology.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Fas-associated protein with death domain (FADD), procaspase-8, and cellular FLICE-inhibitory proteins (cFLIP) assemble through death-effector domains (DEDs), directing death receptor signaling towards cell survival or apoptosis. Understanding their three-dimensional regulatory mechanism has been limited by the absence of atomic coordinates for their ternary DED complex. By employing X-ray crystallography and cryogenic electron microscopy (cryo-EM), we present the atomic coordinates of human FADD-procaspase-8-cFLIP complexes, revealing structural insights into these critical interactions. These structures illustrate how FADD and cFLIP orchestrate the assembly of caspase-8-containing complexes and offer mechanistic explanations for their role in promoting or inhibiting apoptotic and necroptotic signaling. A helical procaspase-8-cFLIP hetero-double layer in the complex appears to promote limited caspase-8 activation for cell survival. Our structure-guided mutagenesis supports the role of the triple-FADD complex in caspase-8 activation and in regulating receptor-interacting protein kinase 1 (RIPK1). These results propose a unified mechanism for DED assembly and procaspase-8 activation in the regulation of apoptotic and necroptotic signaling across various cellular pathways involved in development, innate immunity, and disease.
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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.