ArticleThe Journal of biological chemistry2014
Dominant negative effects of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor 4 on TRAIL receptor 1 signaling by formation of heteromeric complexes.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Escaping cell death via TRAIL decoy receptors: a systematic review of their roles and expressions in colorectal cancer.Apoptosis : an international journal on programmed cell death · 2022Pooled it
- Realizing the potential of agonistic antibody immunotherapy.Nature reviews. Drug discovery · 2026Review
- Review
- Review
- Targeting Death Receptor 5 (DR5) for the imaging and treatment of primary bone and soft tissue tumors: an update of the literature.Frontiers in molecular biosciences · 2024Review
- Potentiation of TRAIL-Induced Apoptosis in TRAIL-Resistant Cholangiocarcinoma Cells by Curcumin through the Induction of DR5 Membrane Localization and Disruption of the Anti-Apoptotic Complex DR5/DDX3/GSK3β.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- The benefits of clustering in TNF receptor superfamily signaling.Frontiers in immunology · 2023Review
- Endogenous TRAIL-R4 critically impacts apoptotic and non-apoptotic TRAIL-induced signaling in cancer cells.Frontiers in cell and developmental biology · 2022Article
- Mutations in the binding site of TNFR1 PLAD reduce homologous interactions but can enhance antagonism of wild-type TNFR1 activity.Immunology · 2021Article
- NCTRCancer chemotherapy and pharmacology · 2021Article
- TNF receptor agonists induce distinct receptor clusters to mediate differential agonistic activity.Communications biology · 2021Article
- Noncompetitive Allosteric Antagonism of Death Receptor 5 by a Synthetic Affibody Ligand.Biochemistry · 2020Article
- Mechanisms of Apoptosis Resistance to NK Cell-Mediated Cytotoxicity in Cancer.International journal of molecular sciences · 2020Review
- Stress Management: Death Receptor Signalling and Cross-Talks with the Unfolded Protein Response in Cancer.Cancers · 2020Review
- Receptor Oligomerization and Its Relevance for Signaling by Receptors of the Tumor Necrosis Factor Receptor Superfamily.Frontiers in cell and developmental biology · 2020Review
- TRAIL Induces Nuclear Translocation and Chromatin Localization of TRAIL Death Receptors.Cancers · 2019Article
- Molecular Mode of Action of TRAIL Receptor Agonists-Common Principles and Their Translational Exploitation.Cancers · 2019Review
- TRAILblazing Strategies for Cancer Treatment.Cancers · 2019Review
- Death receptor 5 is activated by fucosylation in colon cancer cells.The FEBS journal · 2019Article
- Molecular Biomarkers in Drug-Induced Liver Injury: Challenges and Future Perspectives.Frontiers in pharmacology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytokine TNF-related apoptosis-inducing ligand (TRAIL) and its cell membrane receptors constitute an elaborate signaling system fulfilling important functions in immune regulation and tumor surveillance. Activation of the death receptors TRAILR1 and TRAILR2 can lead to apoptosis, whereas TRAILR3 and TRAILR4 are generally referred to as decoy receptors, which have been shown to inhibit TRAIL-induced apoptosis. The underlying molecular mechanisms, however, remain unclear. Alike other members of the TNF receptor superfamily, TRAIL receptors contain a pre-ligand binding assembly domain (PLAD) mediating receptor oligomerization. Still, the stoichiometry of TRAIL receptor oligomers as well as the issue of whether the PLAD mediates only homotypic or also heterotypic interactions remained inconclusive until now. Performing acceptor-photobleaching FRET studies with receptors 1, 2, and 4, we demonstrate interactions in all possible combinations. Formation of dimers was shown by chemical cross-linking experiments for interactions of TRAILR2 and heterophilic interactions between the two death receptors or between either of the death receptors and TRAILR4. Implications of the demonstrated receptor-receptor interactions on signaling were investigated in suitable cellular models. Both apoptosis induction and activation of the transcription factor NFκB were significantly reduced in the presence of TRAILR4. Our experimental data combined with mathematical modeling show that the inhibitory capacity of TRAILR4 is attributable to signaling-independent mechanisms, strongly suggesting a reduction of signaling competent death receptors through formation heteromeric receptor complexes. In summary, we propose a model of TRAIL receptor interference driven by PLAD-mediated formation of receptor heterodimers on the cell membrane.
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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.