Figure 1. Schematic depiction of the model.

The model characterizes crosstalk between the HIF-1 and p53 pathways upon hypoxia. In hypoxia, HIF-1α is stabilized due to reduced hydroxylation by PHD. Under severe hypoxia, the ATR kinase is activated via auto-phosphorylation upon hypoxia-induced replication arrest, and p53 is further activated by ATR. The shared coactivator p300 is required for the full transcriptional activity of p53 and HIF-1α. HIF-1α evokes transient cell-cycle arrest via inducing p21, whereas p53 can induce apoptosis via transrepressing or/and transactivating target genes. Dashed lines denote the expression of target genes by HIF-1α or p53, while solid arrowed lines represent the transitions between proteins. Circle- and bar-headed lines denote the promotion and inhibition of transition or production, respectively.