A mathematical model of caspase function in apoptosis

@article{Fussenegger2000AMM,
  title={A mathematical model of caspase function in apoptosis},
  author={M. Fussenegger and J. Bailey and J. Varner},
  journal={Nature Biotechnology},
  year={2000},
  volume={18},
  pages={768-774}
}
Caspases (cysteine-containing aspartate-specific proteases) are at the core of the cell's suicide machinery. These enzymes, once activated, dismantle the cell by selectively cleaving key proteins after aspartate residues. The events culminating in caspase activation are the subject of intense study because of their role in cancer, and neurodegenerative and autoimmune disorders. Here we present a mechanistic mathematical model, formulated on the basis of newly emerging information, describing… Expand
Mathematical modeling of the formation of apoptosome in intrinsic pathway of apoptosis
TLDR
This study mathematically model caspase-9 activation by using a system of ordinary differential equations (an ODE model) generated by a systems biology tool Simpathica—a simulation and reasoning system, developed to study biological pathways. Expand
A mathematical model for apoptosome assembly: the optimal cytochrome c/Apaf-1 ratio.
TLDR
A mathematical model is constructed for Apaf-1 heptamer assembly process that reveals that intermediate products can remain unconverted even after all assemble reactions are completed, and the optimal number of subunits comprising an active oligomer that maximize the conversion efficiency in assembly process, and found that the tetramer is the optimum. Expand
The molecular mechanism of apoptosis upon caspase-8 activation: quantitative experimental validation of a mathematical model.
TLDR
This work systematically investigated the caspase cascade by regulating the magnitude of extrinsic signals received by the cell, and validated a mathematical model suitable for estimation of the kinetics and dynamics of caspases, which predicts the minimal concentration of CASP8 required to act as an initiator. Expand
Bistability Analyses of a Caspase Activation Model for Receptor-induced Apoptosis*
TLDR
The current knowledge of the molecular mechanisms of the death-receptor-activated caspase cascade is translated into a mathematical model and a reduction down to the apoptotic core machinery enables the application of analytical mathematical methods to evaluate the system behavior within a wide range of parameters. Expand
Dynamics of granzyme B-induced apoptosis: mathematical modeling.
TLDR
The dynamics of caspase activation and target cleavage in apoptosis induced by granzyme B in a single K562 cell was studied using a mathematical model of the dynamics of gran enzyme B-induced apoptosis developed in this work. Expand
Estimating parameters in the caspase-activated apoptosis system
Owing to their role in several diseases, the caspase activated apoptosis system has been paid much attention in recent years. Based on mass-conservation principle and kinetic rate law, a system ofExpand
Mathematical modelling of the mitochondrial apoptosis pathway.
TLDR
The currently applied modelling approaches are described, the suitability of different modelling techniques are discussed, and their contribution to the understanding of the mitochondrial apoptosis pathway is evaluated. Expand
Experimental testing of a mathematical model relevant to the extrinsic pathway of apoptosis
TLDR
The results of in vitro experiments aimed at revealing the dynamics of caspase activation in a cell population are reported and a qualitative agreement between these results and a mathematical model describing a pathway from an external stimulus to caspases activation was obtained, showing that the model captures the essential features of the biological process and may be a reliable tool in further studies of casing activation. Expand
A Mathematical Model of Fas Signaling Induced Apoptosis
TLDR
This study investigates Fas-induced apoptosis, and establishes a mathematical model without the requirement of bistability that reveals a pulse increasing of caspase-3 activation following FasL stimulation to trigger the irreversible death program. Expand
Systems Biology of the Mitochondrial Apoptosis Pathway
Mitochondria have multiple functions. Apart from their role in the regulation of cellular bioenergetics, redox homeostasis and signal transduction, mitochondria are able to initiate apoptosis. TheExpand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 38 REFERENCES
Casper is a FADD- and caspase-related inducer of apoptosis.
TLDR
A C-terminal deletion mutant of Casper inhibits TNF- and Fas-induced cell death, suggesting that Casper is involved in these apoptotic pathways. Expand
Caspase activation: the induced-proximity model.
  • G. Salvesen, V. Dixit
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1999
TLDR
Evidence for a hypothesis-the induced-proximity model-that describes how the first proteolytic signal is produced after adapter-mediated clustering of initiator caspase zymogens is reviewed. Expand
Anti-apoptotic oncogenes prevent caspase-dependent and independent commitment for cell death
TLDR
Oncogenesis is promoted not by simply interfering with caspase-mediated apoptosis, but by preventing an upstream event which is defined as the commitment point for cell death. Expand
X-linked IAP is a direct inhibitor of cell-death proteases
TLDR
It is shown that human X-chromosome-linked IAP directly inhibits at least two members of the caspase family of cell-death proteases, caspasing-3 and caspases-7, providing evidence for a mechanism of action for these mammalian cell- death suppressors. Expand
Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade
TLDR
Mutation of the active site of caspase-9 attenuated the activation of cazase-3 and cellular apoptotic response in vivo, indicating that casp enzyme-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP. Expand
Mitochondria and apoptosis.
TLDR
The possibility that the mechanism originally involved in the maintenance of the symbiosis between the bacterial ancestor of the mitochondria and the host cell precursor of eukaryotes provided the basis for the actual mechanism controlling cell survival is discussed. Expand
Apoptosis: Dead end for neurodegeneration?
TLDR
Two studies show that symptoms of Huntington's disease are less severe when caspase-1-mediated cleavage of the huntingtin protein is blocked and the cytoplasmic domain of the beta-amyloid precursor protein is shown to be cleaved directly by caspases, leading to increased production of the amyloid-beta peptide. Expand
IAPs block apoptotic events induced by caspase‐8 and cytochrome c by direct inhibition of distinct caspases
TLDR
It is demonstrated that IAPs can suppress different apoptotic pathways by inhibiting distinct caspases and identify pro‐caspase‐9 as a new target for IAP‐mediated inhibition of apoptosis. Expand
The Bcl-2 protein family: arbiters of cell survival.
Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens. Those most similar toExpand
Caspases: enemies within.
TLDR
This work has shown that understanding caspase regulation is intimately linked to the ability to rationally manipulate apoptosis for therapeutic gain. Expand
...
1
2
3
4
...