Mathematical Modeling of p53 Pathways

Cells have evolved balanced systems that ensure an appropriate response to stress. The systems elicit repair responses in temporary or moderate stress but eliminate irreparable cells via apoptosis in detrimental conditions of prolonged or severe stress. The tumor suppressor p53 is a central player in these stress response systems. When activated under DNA damage stress, p53 regulates hundreds of genes that are involved in DNA repair, cell cycle, and apoptosis. Recently, increasing studies have demonstrated additional regulatory roles of p53 in metabolism and mitochondrial physiology. Due to the inherent complexity of feedback loops between p53 and its target genes, the application of mathematical modeling has emerged as a novel approach to better understand the multifaceted functions and dynamics of p53. In this review, we discuss several mathematical modeling approaches in exploring the p53 pathways.