ArticleCell death & disease2012
The adaptor protein FADD and the initiator caspase-8 mediate activation of NF-κB by TRAIL.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- SETD5 in glioma cells conferred TRAIL resistance induction.Scientific reports · 2025Article
- Caspases: structural and molecular mechanisms and functions in cell death, innate immunity, and disease.Cell discovery · 2025Review
- Cellular Dynamics of Fas-Associated Death Domain in the Regulation of Cancer and Inflammation.International journal of molecular sciences · 2024Review
- Article
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- When cell death goes wrong: inflammatory outcomes of failed apoptosis and mitotic cell death.Cell death and differentiation · 2023Review
- The evolution of regulated cell death pathways in animals and their evasion by pathogens.Physiological reviews · 2022Review
- HS3ST1 Promotes Non-Small-Cell Lung Cancer Progression by Targeting the SPOP/FADD/NF-BioMed research international · 2022Article
- Cell death in head and neck cancer pathogenesis and treatment.Cell death & disease · 2021Review
- Stress-induced TRAILR2 expression overcomes TRAIL resistance in cancer cell spheroids.Cell death and differentiation · 2020Article
- Cell death in the gut epithelium and implications for chronic inflammation.Nature reviews. Gastroenterology & hepatology · 2020Review
- A simplified method for the efficient purification and refolding of recombinant human TRAIL.Biotechnology progress · 2020Article
- Caspase-8-Dependent Inflammatory Responses Are Controlled by Its Adaptor, FADD, and Necroptosis.Immunity · 2020Article
- Auto Arginine-GlcNAcylation Is Crucial for Bacterial Pathogens in Regulating Host Cell Death.Frontiers in cellular and infection microbiology · 2020Article
- Extracellular vesicle-cargo miR-185-5p reflects type II alveolar cell death after oxidative stress.Cell death discovery · 2020Article
- TRAILblazing Strategies for Cancer Treatment.Cancers · 2019Review
- Redundant and receptor-specific activities of TRADD, RIPK1 and FADD in death receptor signaling.Cell death & disease · 2019Article
- Developing TRAIL/TRAIL death receptor-based cancer therapies.Cancer metastasis reviews · 2018Review
- Mind Bomb Regulates Cell Death during TNF Signaling by Suppressing RIPK1's Cytotoxic Potential.Cell reports · 2018Article
- Autophagy as a mechanism of Apo2L/TRAIL resistance.Cancer biology & therapy · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Besides inducing apoptosis, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activates NF-κB. The apoptosis signaling pathway of TRAIL is well characterized involving TRAIL receptors, Fas-associated protein with death domain (FADD) and caspase-8. In contrast, the molecular mechanism of TRAIL signaling to NF-κB remains controversial. Here, we characterized the receptor-proximal mediators of NF-κB activation by TRAIL. Deletion of the DD of TRAIL receptors 1 and 2 revealed that it is essential in NF-κB signaling. Because FADD interacts with the TRAIL receptor DD, FADD was tested. RNAi-mediated knockdown of FADD or FADD deficiency in JURKAT T-cell leukemia cells decreased or disabled NF-κB signaling by TRAIL. In contrast, TRAIL-induced activation of NF-κB was maintained upon loss of receptor interacting protein 1 (RIP1) or knockdown of FLICE-like inhibitory protein (FLIP). Exogenous expression of FADD rescued TRAIL-induced NF-κB signaling. Loss-of-function mutations of FADD within the RHDLL motif of the death effector domain, which is required for TRAIL-induced apoptosis, abrogated FADD's ability to recruit caspase-8 and mediate NF-κB activation. Accordingly, deficiency of caspase-8 inhibited TRAIL-induced activation of NF-κB, which was rescued by wild-type caspase-8, but not by a catalytically inactive caspase-8 mutant. These data establish the mechanism of TRAIL-induced NF-κB activation involving the TRAIL receptor DD, FADD and caspase-8, but not RIP1 or FLIP. Our results show that signaling of TRAIL-induced apoptosis and NF-κB bifurcates downstream of caspase-8.
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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.