Simulation Of P53 Dynamic Behavior Under Ionizing Radiation

For normal cells,ionizing radiation is a strong killing method,it causes double-strand breaks in DNA,which is a kind of difficult-to-heal damage that easily triggers apoptosis.How-ever,for cancer cells,due to the imperfect apoptotic system,they show strong vitality and can usually avoid spontaneous death.Tumor suppressor p53 is one of the most commonly mutated genes in cancer,it regulates a variety of downstream genes,some of these downstream genes are responsible for cell repair and some are responsible for programmed cell apoptosis.The dy-namic behavior of p53 is closely related to cell fate,under ionizing radiation,p53 in some cells tends to reach higher levels,and p53 in some cells is more prone to continuous pulses.High levels of p53 are conducive to the apoptosis gene and induce apoptosis.Under the continuous p53 pulse,cells not only have no apoptosis,but can even maintain proliferationWe first studied an abstract p53-mdm2 small model extracted from a p53 network.Using theoretical derivation and numerical calculations,we found an important reason for p53 os-cillation,which is the self-catalyzed degradation of mdm2.In addition,previous studies have shown that the oscillation of p53 in cancer cells is closely related to the activity of the protein kinase Akt.Activated Akt promotes the negative regulator of p53,mdm2,to enter the nucleus,forming a p53-mdm2 negative feedback loop,providing a basic structure for p53 oscillation The participation of the phosphatase Wipl ensures a uniform shape of the p53 pulse.In normal cells,Akt activity is co-regulated by growth factors and phosphatase PTEN,which is activated to an appropriate degree to maintain normal metabolism.Cancer cells lack PTEN expression on the one hand,and are overly sensitive to growth factors on the other hand,leading to Akt overactivation.Based on the above considerations,we have studied the deterministic model of the complete response network of p53 under ionizing radiation.