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          Institute: MPI für Dynamik komplexer technischer Systeme     Collection: Systems Biology     Display Documents



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ID: 207899.0, MPI für Dynamik komplexer technischer Systeme / Systems Biology
Bistability Analyses of a Caspase Activation Model for Receptor-induced Apoptosis
Authors:Eissing, T.; Conzelmann, H.; Gilles, E. D.; Allgöwer, F.; Bullinger, E.; Scheurich, P.
Language:English
Date of Publication (YYYY-MM-DD):2004
Title of Journal:The Journal of Biological Chemistry
Volume:279
Start Page:36892
End Page:36897
Review Status:not specified
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Apoptosis is an important physiological process crucially involved in development and homeostasis of multicellular organisms. Although the major signaling pathways have been unraveled, a detailed mechanistic understanding of the complex underlying network remains elusive. We have translated here the current knowledge of the molecular mechanisms of the death-receptor-activated caspase cascade into a mathematical model. 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. Using parameter values from the literature, the model reveals an unstable status of survival indicating the need for further control. Based on recent publications we tested one additional regulatory mechanism at the level of initiator caspase activation and demonstrated that the resulting system displays desired characteristics such as bistability. In addition, the results from our model studies allowed us to reconcile the fast kinetics of caspase 3 activation observed at the single cell level with the much slower kinetics found at the level of a cell population.
External Publication Status:published
Document Type:Article
Communicated by:Ernst-Dieter Gilles
Affiliations:MPI für Dynamik komplexer technischer Systeme/Systems Biology
Identifiers:LOCALID:983 29/04
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