Figure 1.

Schematic diagram of the model for p53-mediated cell-fate decision after DNA damage. There exist two p53-centered feedback loops, i.e., the p53-Mdm2 negative feedback loop and the p53-PTEN-Akt-Mdm2 positive feedback loop. Hzf and ASPP, the cofactors of p53, are induced by p53 and E2F1, respectively. Hzf is degraded by an unknown E3 ligase, which may be separately induced by E2F1 or p53 in two schemes (labeled as 1 and 2). p53 triggers cell cycle arrest and apoptosis through p21 and Bax, respectively. There exists a positive feedback loop between cytochrome c (CytoC) release and caspase-3 (Casp3) activation. (Dashed lines) Transactivation of target genes by p53 and E2F1. (Arrow-headed solid lines) State transition; (circle-headed and bar-headed lines) promotion and inhibition of state transition. (Arrow-headed double lines) Other processes.