Partial equilibrium approximations in apoptosis. II. The death-inducing signaling complex subsystem

• We apply the PEA method to simplify the Fas-induced apoptotic pathway model.
• We simplify the model from 35 reactions (26 species) to 6 reactions (9 species).
• Numerical simulations show the reliability of the simplified model.
• The simplified model reveals the key reactants and dominated pathways.

This paper is a continuation of our previous work (Huang and Yong, 2013) for simplifying the Fas signaling-induced apoptotic pathway identified by Hua et al. (2005) for human tumor T cells. The previous paper studied the downstream intracelluar-signaling subsystem, while the present one is concerned with the upstream death-inducing signaling complex (DISC) subsystem. Under the assumption that the bind of Fas-associated death domains and FLICE-inhibitory proteins to the DISC is much faster than that of the initiator procaspases, we greatly simplify the upstream subsystem from 35 reactions with 26 species to 6 reactions with 9 species by adopting the classical and recently justified partial equilibrium approximation method. Numerical simulations show that the simplified model is in an excellent agreement with the original model. Most importantly, the simplified model clearly reveals the key reactants and dominated pathways in the Fas signaling process, and thus provides new insights into the apoptosis.