ArticleScientific reports2021
BAX and SMAC regulate bistable properties of the apoptotic caspase system.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Glycoconjugate strategy for GLUT-driven curcumin delivery and anticancer activity in breast cancer cells.Scientific reports · 2026Article
- The second mitochondrial activator of caspases (SMAC) regulates growth, inflammation and mitochondrial integrity in cancer cells.Cell death and differentiation · 2026Article
- The sperm survival switch: circRNA-mediated regulatory loops control apoptotic signalling in human spermatozoa.Cell death discovery · 2026Article
- Endogenous Network Modeling Reveals Mechanisms of Repair Schwann Cell Decline and Potential Recovery Targets.Biology · 2026Article
- Review
- Microglial Necroptosis Mediated by RIPK3 Leads to Retinal Ganglion Cell Apoptosis Through the Release of FGF2 After Ischemia/Reperfusion.Journal of molecular neuroscience : MN · 2025Article
- Exploring the omnigenic architecture of selected complex traits.American journal of human genetics · 2025Article
- Article
- Engineering of the Caspase-3 Gene in Recombinant CHO Cells Caused More Apoptosis Resistance and enhanced Recombinant Protein Production Than the BAX Gene.Iranian biomedical journal · 2025Article
- Quercetin triggers cell apoptosis-associated ROS-mediated cell death and induces S and G2/M-phase cell cycle arrest in KON oral cancer cells.BMC complementary medicine and therapies · 2025Article
- Smac/DIABLO protein acts as an independent prognostic factor in oral squamous cell carcinoma.Scientific reports · 2024Article
- Complex IIa formation and ABC transporters determine sensitivity of OSCC to Smac mimetics.Cell death & disease · 2024Article
- Evaluating the Mechanism of Cell Death in Melanoma Induced by the Cannabis Extract PHEC-66.Cells · 2024Article
- Design and mathematical analysis of activating transcriptional amplifiers that enable modular temporal control in synthetic juxtacrine circuits.Synthetic and systems biotechnology · 2023Article
- Origin, heterogeneity, and interconversion of noncanonical bistable switches from the positive feedback loops under dual signaling.iScience · 2023Article
- Cell state-directed therapy - epigenetic modulation of gene transcription demonstrated with a quantitative systems pharmacology model of temozolomide.CPT: pharmacometrics & systems pharmacology · 2023Article
- Cell survival following direct executioner-caspase activation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Interaction of LATS1 with SMAC links the MST2/Hippo pathway with apoptosis in an IAP-dependent manner.Cell death & disease · 2022Article
- Article
- Effects ofFrontiers in pharmacology · 2022Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The initiation of apoptosis is a core mechanism in cellular biology by which organisms control the removal of damaged or unnecessary cells. The irreversible activation of caspases is essential for apoptosis, and mathematical models have demonstrated that the process is tightly regulated by positive feedback and a bistable switch. BAX and SMAC are often dysregulated in diseases such as cancer or neurodegeneration and are two key regulators that interact with the caspase system generating the apoptotic switch. Here we present a mathematical model of how BAX and SMAC control the apoptotic switch. Formulated as a system of ordinary differential equations, the model summarises experimental and computational evidence from the literature and incorporates the biochemical mechanisms of how BAX and SMAC interact with the components of the caspase system. Using simulations and bifurcation analysis, we find that both BAX and SMAC regulate the time-delay and activation threshold of the apoptotic switch. Interestingly, the model predicted that BAX (not SMAC) controls the amplitude of the apoptotic switch. Cell culture experiments using siRNA mediated BAX and SMAC knockdowns validated this model prediction. We further validated the model using data of the NCI-60 cell line panel using BAX protein expression as a cell-line specific parameter and show that model simulations correlated with the cellular response to DNA damaging drugs and established a defined threshold for caspase activation that could distinguish between sensitive and resistant melanoma cells. In summary, we present an experimentally validated dynamic model that summarises our current knowledge of how BAX and SMAC regulate the bistable properties of irreversible caspase activation during apoptosis.
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