Simulation-Based Validation of the p53 Transcriptional Activity with Hybrid Functional Petri Net - Biological Petri Nets - page 137

Fig. 3. Simulation results of concentration behaviors of p53(N), MDM2(N), p19ARF(N), p53 MDM2 p19ARF, and Bax mRNA
on combinations of p53 , MDM2 , and p19ARF overexpressions. + ; overexpress the corresponding gene, -; not overexpress the
corresponding gene. Transition of T 5 , T 12 , and T 14 incorporates to the HFPN model for representing the overexpression of
p53 , MDM2 , and p19ARF . Each of these transitions is removed from the HFPN model in the case of no overexpression of the
corresponding gene.
5. The complex p53-MDM2-p19ARF can activate genes MDM2 and Bax , while all of genes p53 ,
MDM2 , and p19ARF are expressed.
When none of three genes p53 , MDM2 , and p19ARF is expressed, the concentrations of p53(N),
MDM2(N), p19ARF(N), p53 MDM2 p19ARF, and Bax mRNA do not grow (Fig. 3(1)). When gene
p53 is expressed, protein p53 in the nucleus (p53(N)) shows a temporal high concentration, and thereafter
keeps its concentration at a lower level (Fig. 3(2)). Low accumulation of MDM2(N) in the nucleus and
low expression of Bax mRNA are also observed.