ArticleMolecular systems biology2011
Lyapunov exponents and phase diagrams reveal multi-factorial control over TRAIL-induced apoptosis.
Article in Molecular systems biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 2 citations in OpenAlex.
- Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025Review
- Pharmacological targeting of caspase-8/c-FLIPCommunications biology · 2025Article
- Cell survival following direct executioner-caspase activation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Two-level modeling approach to identify the regulatory dynamics capturing drug response heterogeneity in single-cells.Scientific reports · 2021Article
- TNF controls a speed-accuracy tradeoff in the cell death decision to restrict viral spread.Nature communications · 2021Article
- Convergence of pathway analysis and pattern recognition predicts sensitization to latest generation TRAIL therapeutics by IAP antagonism.Cell death and differentiation · 2020Article
- Interplay Between Mitophagy and Apoptosis Defines a Cell Fate Upon Co-treatment of Breast Cancer Cells With a Recombinant Fragment of Human κ-Casein and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand.Frontiers in cell and developmental biology · 2020Article
- A Probabilistic Approach to Explore Signal Execution Mechanisms With Limited Experimental Data.Frontiers in genetics · 2020Article
- System-based approaches as prognostic tools for glioblastoma.BMC cancer · 2019Review
- Mathematical Modeling Highlights the Complex Role of AKT in TRAIL-Induced Apoptosis of Colorectal Carcinoma Cells.iScience · 2019Article
- Co-imaging extrinsic, intrinsic and effector caspase activity by fluorescence anisotropy microscopy.Redox biology · 2018Article
- Article
- Dual role of DR5 in death and survival signaling leads to TRAIL resistance in cancer cells.Cell death & disease · 2017Article
- A data-driven modeling approach to identify disease-specific multi-organ networks driving physiological dysregulation.PLoS computational biology · 2017Article
- Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo.BMC systems biology · 2015Article
- Surviving apoptosis: life-death signaling in single cells.Trends in cell biology · 2015Review
- Apoptosis Triggers Specific, Rapid, and Global mRNA Decay with 3' Uridylated Intermediates Degraded by DIS3L2.Cell reports · 2015Article
- Modeling dynamics of cell-to-cell variability in TRAIL-induced apoptosis explains fractional killing and predicts reversible resistance.PLoS computational biology · 2014Article
- ODE constrained mixture modelling: a method for unraveling subpopulation structures and dynamics.PLoS computational biology · 2014Article
- Cell-to-cell variability in cell death: can systems biology help us make sense of it all?Cell death & disease · 2014Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Receptor-mediated apoptosis proceeds via two pathways: one requiring only a cascade of initiator and effector caspases (type I behavior) and the second requiring an initiator-effector caspase cascade and mitochondrial outer membrane permeabilization (type II behavior). Here, we investigate factors controlling type I versus II phenotypes by performing Lyapunov exponent analysis of an ODE-based model of cell death. The resulting phase diagrams predict that the ratio of XIAP to pro-caspase-3 concentrations plays a key regulatory role: type I behavior predominates when the ratio is low and type II behavior when the ratio is high. Cell-to-cell variability in phenotype is observed when the ratio is close to the type I versus II boundary. By positioning multiple tumor cell lines on the phase diagram we confirm these predictions. We also extend phase space analysis to mutations affecting the rate of caspase-3 ubiquitylation by XIAP, predicting and showing that such mutations abolish all-or-none control over activation of effector caspases. Thus, phase diagrams derived from Lyapunov exponent analysis represent a means to study multi-factorial control over a complex biochemical pathway.
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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.