FIGURE 4.

Numerical solution of a two-compartment-based TNF-stimulated feed-forward NF-κB model. A, the schematic model represents both canonical and non-canonical pathways coupled by TRAF1 dynamics. n represents nuclear protein. Each reaction is represented by a kinetic parameter (Table 2). UNK: unknown NIK promoter. B, shown are kinetic time profiles of NF-κB-dependent TRAF1 and TRAF2 proteins in the canonical pathway. C, shown are kinetic time profiles of NF-κB-dependent p100 and its processing to p52; a time evolution of newly synthesized p100 is shown here that increases with time. The proteolytic processing of p100 leads to the generation of p52 (cytoplasmic), which then translocates into nucleus (p52n) using an import-export mechanism as mentioned in Table 2. D, shown are kinetic time profiles of the activation complex of TRAF1·NIK and its involvement in non-canonical activation; the inducible TRAF1-mediated NIK stabilization activates the p100 processing mechanism to produce p52. The nuclear p52 then binds to promoters of non-canonical genes such as Naf1 to initiate its transcription.