ArticleEMBO reports2020
A revised model of TRAIL-R2 DISC assembly explains how FLIP(L) can inhibit or promote apoptosis.
Article in EMBO reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- REDD1/DDIT4 counteracts endoplasmic reticulum stress-induced apoptosis by controlling the expression of death receptor TRAILR2/DR5 in cancer cells.Cell death & disease · 2026Article
- Research landscape of photodynamic therapy for hepatocellular carcinoma: Hotspots and Prospects from 2012 to 2025.Hereditas · 2025Review
- Activation of the integrated stress response and loss of cFLIPCell death discovery · 2025Article
- Turn TRAIL Into Better Anticancer Therapeutic Through TRAIL Fusion Proteins.Cancer medicine · 2025Review
- Review
- Reverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes.Nature communications · 2024Article
- Caspase-8 in inflammatory diseases: a potential therapeutic target.Cellular & molecular biology letters · 2024Review
- cFLIP in the molecular regulation of astroglia-driven neuroinflammation in experimental glaucoma.Journal of neuroinflammation · 2024Article
- Deciphering DED assembly mechanisms in FADD-procaspase-8-cFLIP complexes regulating apoptosis.Nature communications · 2024Article
- Review
- Caloric restriction leads to druggable LSD1-dependent cancer stem cells expansion.Nature communications · 2024Article
- Article
- Review
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- The benefits of clustering in TNF receptor superfamily signaling.Frontiers in immunology · 2023Review
- Limiting glutamine utilization activates a GCN2/TRAIL-R2/Caspase-8 apoptotic pathway in glutamine-addicted tumor cells.Cell death & disease · 2022Article
- Review
- Induction of Breast Cancer Cell Apoptosis by TRAIL and Smac Mimetics: Involvement of RIP1 and cFLIP.Current issues in molecular biology · 2022Article
- Restoring TRAILR2/DR5-Mediated Activation of Apoptosis upon Endoplasmic Reticulum Stress as a Therapeutic Strategy in Cancer.International journal of molecular sciences · 2022Review
- Functional Genomic Identification of Predictors of Sensitivity and Mechanisms of Resistance to Multivalent Second-Generation TRAIL-R2 Agonists.Molecular cancer therapeutics · 2022Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
The long FLIP splice form FLIP(L) can act as both an inhibitor and promoter of caspase-8 at death-inducing signalling complexes (DISCs) formed by death receptors such as TRAIL-R2 and related intracellular complexes such as the ripoptosome. Herein, we describe a revised DISC assembly model that explains how FLIP(L) can have these opposite effects by defining the stoichiometry (with respect to caspase-8) at which it converts from being anti- to pro-apoptotic at the DISC. We also show that in the complete absence of FLIP(L), procaspase-8 activation at the TRAIL-R2 DISC has significantly slower kinetics, although ultimately the extent of apoptosis is significantly greater. This revised model of DISC assembly also explains why FLIP's recruitment to the TRAIL-R2 DISC is impaired in the absence of caspase-8 despite showing that it can interact with the DISC adaptor protein FADD and why the short FLIP splice form FLIP(S) is the more potent inhibitor of DISC-mediated 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.