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

Triggering the apoptosis process.

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.

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.

Cleavage/activation of procaspase-2 is confirmed by the experimental data.

Caspase-3 activation plays a crucial role in the cleavage of procaspases-2, -8 and PARP.

PARP inactivation is confirmed by the experimental measurements of PARP and cPARP concentrations.

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).

Production of blocked p43/p41, whose concentration is detected by the experimental data.

Activation of Bid and cleavage of procaspases-7 and −9. These reactions determine dynamics of the mentioned species in agreement with the experimental data.

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*.

The virtual variable x _aa specifies the process of degradation.