ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
The role of TRADD in TRAIL-induced apoptosis and signaling.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 59 citations in OpenAlex.
- Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond.Cellular & molecular immunology · 2025Review
- Blockade of IKK signaling induces RIPK1-independent apoptosis in human macrophages.PLoS pathogens · 2024Article
- Review
- Immunophenotypic and Gene Expression Analyses of the Inflammatory Microenvironment in High-Grade Oral Epithelial Dysplasia and Oral Lichen Planus.Head and neck pathology · 2024Article
- Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis.Frontiers in pharmacology · 2024Review
- A renal YY1-KIM1-DR5 axis regulates the progression of acute kidney injury.Nature communications · 2023Article
- Review
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- Heterogeneity in functional genetic screens: friend or foe?Frontiers in immunology · 2023Review
- Roles of RIPK3 in necroptosis, cell signaling, and disease.Experimental & molecular medicine · 2022Review
- The Most Competent Plant-Derived Natural Products for Targeting Apoptosis in Cancer Therapy.Biomolecules · 2021Review
- Cell death induced by the ER stressor thapsigargin involves death receptor 5, a non-autophagic function of MAP1LC3B, and distinct contributions from unfolded protein response components.Cell communication and signaling : CCS · 2020Article
- HIF1α-mediated TRAIL Expression Regulates Lacrimal Gland Inflammation in Dry Eye Disease.Investigative ophthalmology & visual science · 2020Article
- Functional roles in cell signaling of adaptor protein TRADD from a structural perspective.Computational and structural biotechnology journal · 2020Review
- Redundant and receptor-specific activities of TRADD, RIPK1 and FADD in death receptor signaling.Cell death & disease · 2019Article
- c-FLIP, a Novel Biomarker for Cancer Prognosis, Immunosuppression, Alzheimer's Disease, Chronic Obstructive Pulmonary Disease (COPD), and a Rationale Therapeutic Target.Biomarkers journal · 2019Article
- RIP1 modulates death receptor mediated apoptosis and autophagy in macrophages.Molecular oncology · 2015Article
- Nemo-like kinase (NLK) negatively regulates NF-kappa B activity through disrupting the interaction of TAK1 with IKKβ.Biochimica et biophysica acta · 2014Article
- Apoptosis-associated genes related to photodynamic therapy in breast carcinomas.Lasers in medical science · 2014Article
- Epigonal conditioned media from bonnethead shark, Sphyrna tiburo, induces apoptosis in a T-cell leukemia cell line, Jurkat E6-1.Marine drugs · 2013Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. TRAIL is promising for anticancer therapy because it induces apoptosis in cancer cells with little or no toxicity to normal cells; hence, TRAIL-receptor agonists are currently undergoing clinical trials for cancer treatment. However, many molecular signaling mechanisms in TRAIL signaling are not completely characterized. The functions of adaptor proteins, including TNF-receptor-associated death domain protein (TRADD) and receptor-interacting protein-1 (RIP1) in TRAIL signaling have been controversial. We demonstrate that while wild-type mouse embryonic fibroblasts (MEFs) are completely resistant to TRAIL-induced apoptosis, MEFs derived from Tradd(-/-) mice are hypersensitive to TRAIL (IC(50)~0.5 nM rmTRAIL, 24 h), an effect also seen in primary keratinocytes treated with TRAIL/CHX. Restoration of TRADD in Tradd(-/-) MEFs restores TRAIL resistance, indicating that TRADD plays a survival role in TRAIL signaling. We show that TRADD is recruited to the TRAIL-receptor complex, and RIP1 recruitment is mediated by TRADD. While early activation of the MAP kinase ERK is deficient in Tradd(-/-) cells, the main mechanism for enhanced TRAIL sensitivity is likely due to increased recruitment of FADD to the receptor complex, indicating that TRADD may limit FADD binding within the receptor complex and also mediate RIP1-dependent nonapoptotic signaling events, thus reducing caspase activation and subsequent apoptosis. These novel findings have potential implications for cancer therapy using TRAIL-receptor agonists.
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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.