ArticleOncogene2003
Ceramide-mediated clustering is required for CD95-DISC formation.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 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
109 citing papers in PubMed, 267 citations in OpenAlex.
- Review
- A novel prenylflavonoid with efficacy in cancer therapy by targeting ceramide-orchestrated signaling.Frontiers in pharmacology · 2026Article
- Murine Models of Obesity-Related Cancer Risk.Cancer prevention research (Philadelphia, Pa.) · 2025Review
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Using ultrasound and microbubble to enhance the effects of conventional cancer therapies in clinical settings.Cancer metastasis reviews · 2025Review
- Ceramide microdomains: the major influencers of the sphingolipid media platform.Biochemical Society transactions · 2024Review
- Emerging role of sphingolipids and extracellular vesicles in development and therapeutics of cardiovascular diseases.International journal of cardiology. Heart & vasculature · 2024Review
- Membrane Epilipidome-Lipid Modifications, Their Dynamics, and Functional Significance.Cold Spring Harbor perspectives in biology · 2024Review
- The lipid basis of cell death and autophagy.Autophagy · 2024Review
- Mass Spectrometry Detects Sphingolipid Metabolites for Discovery of New Strategy for Cancer Therapy from the Aspect of Programmed Cell Death.Metabolites · 2023Review
- Dying in self-defence: a comparative overview of immunogenic cell death signalling in animals and plants.Cell death and differentiation · 2023Review
- A genome-wide CRISPR screen implicates plasma membrane asymmetry in exogenous C6-ceramide toxicity.Biology open · 2022Article
- Article
- Clusters of apoptotic signaling molecule-enriched rafts, CASMERs: membrane platforms for protein assembly in Fas/CD95 signaling and targets in cancer therapy.Biochemical Society transactions · 2022Article
- Involvement of Ceramide Signalling in Radiation-Induced Tumour Vascular Effects and Vascular-Targeted Therapy.International journal of molecular sciences · 2022Review
- You aren't IMMUNE to the ceramides that accumulate in cardiometabolic disease.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2022Article
- Anticancer Effects of New Ceramides Isolated from the Red Sea Red AlgaeMarine drugs · 2022Article
- Sphingomyelinase-Mediated Multitimescale Clustering of Ganglioside GM1 in Heterogeneous Lipid Membranes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Inhaled sphingosine has no adverse side effects in isolated ventilated and perfused pig lungs.Scientific reports · 2021Article
- Review
49 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
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Early events required for induction of apoptosis by CD95 are preassociation of CD95, the formation of the death-inducing signaling complex (DISC) and clustering of CD95 in distinct membrane domains. Here, we identify the molecular ordering of these events and show that the acid sphingomyelinase (ASM) functions upstream of the DISC to mediate CD95 clustering in ceramide-enriched membrane platforms, an event that is required for DISC formation. Experiments in ASM-deficient cells revealed that CD95 ligation, in the absence of ceramide generation, triggers <1% of full caspase 8 activation at the receptor. This event, however, is both necessary and sufficient to trigger translocation of ASM onto the outer leaflet of the plasma membrane, ASM activation and ceramide release, but insufficient for apoptosis induction. Ceramide-mediated CD95 clustering then amplifies the primary CD95 signaling and drives the second step of CD95 signaling, that is, formation of the DISC yielding 100% caspase activity and apoptosis. These studies suggest that the most parsimonious interpretation of the molecular ordering of the earliest events in CD95 signaling, at least in some cells, is: CD95 ligation-->1% of maximum caspase 8 activation-->ASM translocation-->ceramide generation-->CD95 clustering-->DISC formation-->100% of maximum caspase 8 activation-->apoptosis.
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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.