Mathematical modeling of the formation of apoptosome in intrinsic pathway of apoptosis

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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URL: http://www.ncbi.nlm.nih.gov/pubmed/19333786
DOI: 10.1007/s11693-009-9022-y

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: http://repository.cshl.edu/id/eprint/27567

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