2004/06/19 by Thomas Eißing, H. Conzelmann, Ernst Dieter Gilles +3 · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Cell death mechanisms and regulation #Receptor Mechanisms and Signaling #Protein Kinase Regulation and GTPase Signaling #Apoptosis #Bistability #Caspase #Cell biology #Cancer research #Caspase 3 #Chemistry #Medicine #Biology #Materials science #Programmed cell death #Optoelectronics #Biochemistry
paper · pdf · doi:10.1074/jbc.m404893200
openalex publication_date 2004/06/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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.