ArticleCell2019
Higher-Order Clustering of the Transmembrane Anchor of DR5 Drives Signaling.
Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
76 citing papers in PubMed, 147 citations in OpenAlex.
- Safety and Efficacy of HexaBody-DR5/DR5 in Malignant Solid Tumors: Phase 1/2a Results and Translational Insights Into Observed Hepatotoxicity.Clinical and translational science · 2026Trial
- Erythrocyte patch for enhanced B cell depletion therapy.Science advances · 2026Article
- Article
- βIII-tubulin can act as a brake on extrinsic apoptosis in pancreatic cancer.Cell death & disease · 2026Article
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- Spontaneous switching in a protein signalling array reveals near-critical cooperativity.Nature physics · 2026Article
- Transmembrane association of DDR1 and DDR2 mediated by Leucine zipper motifs.Magnetic resonance letters · 2025Article
- Engineering hybrid nanoparticles for targeted codelivery of triptolide andScience advances · 2025Article
- DR5 Disulfide Bonding Functions as a Sensor and Effector of Protein Folding Stress.Molecular cancer research : MCR · 2025Article
- Article
- Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancer.Cell reports. Medicine · 2025Article
- Cell-Free Expression of Nipah Virus Transmembrane Proteins for Proteoliposome Vaccine Design.ACS nano · 2025Article
- Solid-state NMR of membrane peptides and proteins in the lipid cubic phase.Biophysical journal · 2025Article
- Comparison of antibody-scTRAIL Fc fusion proteins with varying valency for EGFR and TRAIL receptors.Scientific reports · 2025Article
- The integrated stress response engages a cell-autonomous, ligand-independent, DR5-driven apoptosis switch.Cell death & disease · 2025Article
- Regulation of ER stress-induced apoptotic and inflammatory responses via YAP/TAZ-mediated control of the TRAIL-R2/DR5 signaling pathway.Cell death discovery · 2025Article
- DNA nanoswitches pack an anti-cancer punch.Nature nanotechnology · 2024Article
- PTPN23-dependent ESCRT machinery functions as a cell death checkpoint.Nature communications · 2024Article
- A DNA robotic switch with regulated autonomous display of cytotoxic ligand nanopatterns.Nature nanotechnology · 2024Article
- Cell surface patching via CXCR4-targeted nanothreads for cancer metastasis inhibition.Nature communications · 2024Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Receptor clustering on the cell membrane is critical in the signaling of many immunoreceptors, and this mechanism has previously been attributed to the extracellular and/or the intracellular interactions. Here, we report an unexpected finding that for death receptor 5 (DR5), a receptor in the tumor necrosis factor receptor superfamily, the transmembrane helix (TMH) alone in the receptor directly assembles a higher-order structure to drive signaling and that this structure is inhibited by the unliganded ectodomain. Nuclear magnetic resonance structure of the TMH in bicelles shows distinct trimerization and dimerization faces, allowing formation of dimer-trimer interaction networks. Single-TMH mutations that disrupt either trimerization or dimerization abolish ligand-induced receptor activation. Surprisingly, proteolytic removal of the DR5 ectodomain can fully activate downstream signaling in the absence of ligand. Our data suggest a receptor activation mechanism in which binding of ligand or antibodies to overcome the pre-ligand autoinhibition allows TMH clustering and thus signaling.
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What OpenQuestion holds
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.