Ryu, S., Lin, S. c., Ugel, N., Antoniotti, M., Mishra, B. (June 2008) Mathematical modeling of the formation of apoptosome in intrinsic pathway of apoptosis. Systems and Synthetic Biology, 2 (1). pp. 49-66.
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Abstract
Caspase-9 is the protease that mediates the intrinsic pathway of apoptosis, a type of cell death. Activation of caspase-9 is a multi-step process that requires dATP or ATP and involves at least two proteins, cytochrome c and Apaf-1. In this study, we 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. A rudimentary version of “model checking” based on comparing simulation data with that obtained from a recombinant system of caspase-9 activation, provided several new insights into regulation of this protease. The model predicts that the activation begins with binding of dATP to Apaf-1, which initiates the interaction between Apaf-1 and cytochrome c, thus forming a complex that oligomerizes into an active caspase-9 holoenzyme via a linear binding model with cooperative interaction rather than through network formation.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Model checking Model comparison and selection Apoptosis Apoptosome Caspase-9 ODE model Computational systems biology |
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions |
| CSHL Authors: | |
| Communities: | CSHL labs > Labeznik lab |
| Depositing User: | Matt Covey |
| Date: | June 2008 |
| Date Deposited: | 26 Feb 2013 15:37 |
| Last Modified: | 26 Feb 2013 15:37 |
| PMCID: | PMC2671592 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27567 |
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