ArticleCancers2019
TRAIL Induces Nuclear Translocation and Chromatin Localization of TRAIL Death Receptors.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- MUDENG, a component of adaptor complex 5, mediates TRAIL- and TMZ-triggered apoptosis in glioblastoma (GBM) via multiple pathways.Apoptosis : an international journal on programmed cell death · 2026Article
- DR5 Governs Compound Exocytosis in Colonic Goblet Cells via TATA-Box Binding Protein-Dependent Bestrophin-2 Transcriptional Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synthetic essentiality of TRAIL/TNFSF10 in VHL-deficient renal cell carcinoma.bioRxiv : the preprint server for biology · 2025Article
- Review
- Immuno-inflammatoryFrontiers in immunology · 2023Article
- Article
- Intracranial delivery of synthetic mRNA to suppress glioblastoma.Molecular therapy oncolytics · 2022Article
- Shuttling of cellular proteins between the plasma membrane and nucleus (Review).Molecular medicine reports · 2022Review
- TRAIL-receptor 2-a novel negative regulator of p53.Cell death & disease · 2021Article
- Review
- Death Receptors DR4 and DR5 Undergo Spontaneous and Ligand-Mediated Endocytosis and Recycling Regardless of the Sensitivity of Cancer Cells to TRAIL.Frontiers in cell and developmental biology · 2021Article
- TRAIL receptors are expressed in both malignant and stromal cells in pancreatic ductal adenocarcinoma.American journal of cancer research · 2021Article
- Genetically Modified DR5-Specific TRAIL Variant DR5-B Revealed Dual Antitumor and Protumoral Effect in Colon Cancer Xenografts and an Improved Pharmacokinetic Profile.Translational oncology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Binding of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to the plasma membrane TRAIL-R1/-R2 selectively kills tumor cells. This discovery led to evaluation of TRAIL-R1/-R2 as targets for anti-cancer therapy, yet the corresponding clinical trials were disappointing. Meanwhile, it emerged that many cancer cells are TRAIL-resistant and that TRAIL-R1/-R2-triggering may lead to tumor-promoting effects. Intriguingly, recent studies uncovered specific functions of long ignored intracellular TRAIL-R1/-R2, with tumor-promoting functions of nuclear (n)TRAIL-R2 as the regulator of let-7-maturation. As nuclear trafficking of TRAIL-Rs is not well understood, we addressed this issue in our present study. Cell surface biotinylation and tracking of biotinylated proteins in intracellular compartments revealed that nTRAIL-Rs originate from the plasma membrane. Nuclear TRAIL-Rs-trafficking is a fast process, requiring clathrin-dependent endocytosis and it is TRAIL-dependent. Immunoprecipitation and immunofluorescence approaches revealed an interaction of nTRAIL-R2 with the nucleo-cytoplasmic shuttle protein Exportin-1/CRM-1. Mutation of a putative nuclear export sequence (NES) in TRAIL-R2 or the inhibition of CRM-1 by Leptomycin-B resulted in the nuclear accumulation of TRAIL-R2. In addition, TRAIL-R1 and TRAIL-R2 constitutively localize to chromatin, which is strongly enhanced by TRAIL-treatment. Our data highlight the novel role for surface-activated TRAIL-Rs by direct trafficking and signaling into the nucleus, a previously unknown signaling principle for cell surface receptors that belong to the TNF-superfamily.
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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.