ArticleNature communications2014
Differential affinity of FLIP and procaspase 8 for FADD's DED binding surfaces regulates DISC assembly.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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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
45 citing papers in PubMed.
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- Article
- Pharmacological Inhibition of cFLIP Targets Breast Cancer Stem Cells.Journal of cancer treatment & diagnosis · 2025Article
- Crystal structure of Fis1 and Bap31 provides information on protein-protein interactions at mitochondria-associated ER membranes.Communications biology · 2025Article
- Biological Functions and Clinical Implications of CFLAR: From Cell Death Mechanisms to Therapeutic Targeting in Immune Regulation.Journal of inflammation research · 2025Review
- Review
- NLRP10 maintains epidermal homeostasis by promoting keratinocyte survival and P63-dependent differentiation and barrier function.Cell death & disease · 2024Article
- Reverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes.Nature communications · 2024Article
- Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis.Nature communications · 2024Article
- Cellular Dynamics of Fas-Associated Death Domain in the Regulation of Cancer and Inflammation.International journal of molecular sciences · 2024Review
- Mediators of necroptosis: from cell death to metabolic regulation.EMBO molecular medicine · 2024Review
- The E3 ubiquitin ligase Itch regulates death receptor and cholesterol trafficking to affect TRAIL-mediated apoptosis.Cell death & disease · 2024Article
- The Identification of New c-FLIP Inhibitors for Restoring Apoptosis in TRAIL-Resistant Cancer Cells.Current issues in molecular biology · 2024Article
- When cell death goes wrong: inflammatory outcomes of failed apoptosis and mitotic cell death.Cell death and differentiation · 2023Review
- Endoplasmic Reticulum Stress Signaling and Neuronal Cell Death.International journal of molecular sciences · 2022Review
- Therapeutic approaches targeting CD95L/CD95 signaling in cancer and autoimmune diseases.Cell death & disease · 2022Review
- An engineered construct of cFLIP provides insight into DED1 structure and interactions.Structure (London, England : 1993) · 2022Article
- PEA-15 engages in allosteric interactions using a common scaffold in a phosphorylation-dependent manner.Scientific reports · 2022Article
- Two-level modeling approach to identify the regulatory dynamics capturing drug response heterogeneity in single-cells.Scientific reports · 2021Article
- Clinical Positioning of the IAP Antagonist Tolinapant (ASTX660) in Colorectal Cancer.Molecular cancer therapeutics · 2021Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Death receptor activation triggers recruitment of FADD, which via its death effector domain (DED) engages the DEDs of procaspase 8 and its inhibitor FLIP to form death-inducing signalling complexes (DISCs). The DEDs of FADD, FLIP and procaspase 8 interact with one another using two binding surfaces defined by α1/α4 and α2/α5 helices, respectively. Here we report that FLIP has preferential affinity for the α1/α4 surface of FADD, whereas procaspase 8 has preferential affinity for FADD's α2/α5 surface. These relative affinities contribute to FLIP being recruited to the DISC at comparable levels to procaspase 8 despite lower cellular expression. Additional studies, including assessment of DISC stoichiometry and functional assays, suggest that following death receptor recruitment, the FADD DED preferentially engages FLIP using its α1/α4 surface and procaspase 8 using its α2/α5 surface; these tripartite intermediates then interact via the α1/α4 surface of FLIP DED1 and the α2/α5 surface of procaspase 8 DED2.
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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.