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Table 2 The role of species and reactions in the apoptotic process described by the reduced model

From: Model composition through model reduction: a combined model of CD95 and NF-κB signaling pathways

Species Reactions The role in the apoptosis process
CD95L br1* Triggering the apoptosis process.
DISC br2* Activation of caspase-8 in the DISC complex. In the case of a high ligand concentration, DISC is a slow species, so reactions br1* and br2* cannot be combined.
caspase-3 br3* Activation of caspase-8 via the negative-feedback loop. When the concentration of CD95L is reduced, the rate of br3* is an order of magnitude higher than the rate of br2*. Thus, activation of caspase-8 is mainly caused by caspase-3.
br8* Cleavage/activation of procaspase-2 is confirmed by the experimental data.
br9* Caspase-3 activation plays a crucial role in the cleavage of procaspases-2, -8 and PARP.
br11* PARP inactivation is confirmed by the experimental measurements of PARP and cPARP concentrations.
cFLIP br4* Inhibition of the DISC complex. cFLIP blocks the activity of DISC preventing a significant increase of caspase-8 concentration. This conclusion is consistent with the observations by Bentele et al. asserting that down-regulation of cFLIP resulted in cell death occurring already upon low concentration of anti-CD95 (1 ng/ml).
DISC:cFLIP:pro8 br5* Production of blocked p43/p41, whose concentration is detected by the experimental data.
  br6*, br7*, br10* Activation of Bid and cleavage of procaspases-7 and −9. These reactions determine dynamics of the mentioned species in agreement with the experimental data.
IAP br12* Inhibition of caspase-3. In the case of the reduced activation scenario, IAP prevents caspase-3 from reaching a significant level and, therefore, blocks significant increase of caspase-8 due to br3*.
x aa br13* The virtual variable x aa specifies the process of degradation.
  1. “Experimental data” in this table refers to the data obtained by Bentele et al.[17].