Figure 1.

The p53 signal network. ATM* relays the DNA damage signal and induces activation of p53 from the inactive state to the active state (p53*). P53* is a transcriptional factor that can effectively promote the production of Mdm2; during that process there are inevitably time delays. Here, the time delay covers the time needed during both Mdm2 transcription and translation, which is recorded as τ. In turn, Mdm2 can bind to p53 and p53*, resulting in enhanced degradation of p53 and p53*. On the other hand, p53* can also activate miR-34a. Subsequently, miR-34a inhibits SIRT1 by promoting the degradation of sirt1 mRNA, which leads to an increase of acetylated p53. In addition, Mdm2 protein is degraded by a mechanism stimulated by ATM*.