modeling of p53 signaling pathway regulation
Loss of genomic stability control is central in cancer development. The regulation of normal responses to DNA damage and other forms of genotoxic stress by p53 pathway, isa key element in maintaining this control. The p53 pathway is disarmed by oncogenic mutations in p53 itself, by increased expression of viral oncoproteins, or by defective upstream regulation of p53 in majority of human tumors. Hence p53 plays a crucial role in the prevention and suppression of tumor development (Vogelstein et al . 2000). Regulation of p53 is done at different levels such as the p53 gene is regulated by MDM2 via a negative feedback loop, or it is phosphorylated by a member of protein kinases namely CDK7, or stabilized by the protein ARF (Lin K. et all 2000). Several computational models have been proposed to simulate the dynamics of p53-MDM2 loops, the p53 transcriptional activity, and the programmed cell death (apoptosis) signaling pathway. However none of the reports represent the complete process that will show the link between p53 regulation, apoptosis and other signaling pathways. In this paper we demonstrate the value of using Petri nets to model, simulate and analyze molecular interactions and mechanisms of p53 signaling pathways.
petri net modeling in biology p53 regulation modeling apoptosis modeling modeling signaling pathway