ArticleMolecular systems biology2015
Fractional killing arises from cell-to-cell variability in overcoming a caspase activity threshold.
Article in Molecular systems biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 145 citations in OpenAlex.
- Resurrection biology: Melatonin as a modulator of anastasis (Review).Molecular medicine reports · 2026Review
- Evasion of cell death despite mitochondrial outer membrane permeabilization: an oncogenic outcome of apoptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Regulated cell death plasticity in cancer: thresholds, reversibility, and therapeutic failure.Journal of translational medicine · 2026Review
- A kinome inhibitor screen implicates adhesion and growth factor signaling in cellular recovery after caspase activation.bioRxiv : the preprint server for biology · 2026Article
- Transition between cell states of sensitivity reveals molecular vulnerability of drug-tolerant cells.Molecular systems biology · 2025Article
- Single-cell dynamics reveal a stress-induced decision between hypertrophy and apoptosis in neonatal rat cardiomyocytes.Journal of molecular and cellular cardiology plus · 2025Article
- Deep learning-based image classification reveals heterogeneous execution of cell death fates during viral infection.Molecular biology of the cell · 2025Article
- Integrating QSP and ML to Facilitate Drug Development and Personalized Medicine.Handbook of experimental pharmacology · 2025Review
- Phenotypical, genotypical and pathological characterization of the moonwalker mouse, a model of ataxia.Neurobiology of disease · 2024Article
- Cell cycle plasticity underlies fractional resistance to palbociclib in ER+/HER2- breast tumor cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Density physics-informed neural networks reveal sources of cell heterogeneity in signal transduction.Patterns (New York, N.Y.) · 2024Article
- Article
- Optimal inference of molecular interaction dynamics in FRET microscopy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Model certainty in cellular network-driven processes with missing data.PLoS computational biology · 2023Article
- Cell survival following direct executioner-caspase activation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Characterization of cell-to-cell variation in nuclear transport rates and identification of its sources.iScience · 2023Article
- Modeling Cellular Signaling Variability Based on Single-Cell Data: The TGFβ-SMAD Signaling Pathway.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Coupling live-cell imaging andSTAR protocols · 2022Article
- Cellular Environment and Phenotypic Heterogeneity: How Data-Driven Modeling Finds the Smoking Gun.International journal of molecular sciences · 2022Article
- Systematic inference identifies a major source of heterogeneity in cell signaling dynamics: The rate-limiting step number.Science advances · 2022Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
When cells are exposed to death ligands such as TRAIL, a fraction undergoes apoptosis and a fraction survives; if surviving cells are re-exposed to TRAIL, fractional killing is once again observed. Therapeutic antibodies directed against TRAIL receptors also cause fractional killing, even at saturating concentrations, limiting their effectiveness. Fractional killing arises from cell-to-cell fluctuations in protein levels (extrinsic noise), but how this results in a clean bifurcation between life and death remains unclear. In this paper, we identify a threshold in the rate and timing of initiator caspase activation that distinguishes cells that live from those that die; by mapping this threshold, we can predict fractional killing of cells exposed to natural and synthetic agonists alone or in combination with sensitizing drugs such as bortezomib. A phenomenological model of the threshold also quantifies the contributions of two resistance genes (c-FLIP and Bcl-2), providing new insight into the control of cell fate by opposing pro-death and pro-survival proteins and suggesting new criteria for evaluating the efficacy of therapeutic 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.