Fig. 8. The p53 and PI3K pathways regulate one another. p53 positively regulates PTEN levels, which reverse PI3K action by dephosphorylating PtdIns(3,4,5)P₃ (Stambolic et al., 2001). Our contribution to this figure is in bold with an asterisk: this study demonstrates that p53 directly regulates PIK3CA transcription, resulting in decreased p110 and thus PtdIns(3,4,5)P₃ levels. PtdIns(3,4,5)P₃ recruits AKT to the membrane, where AKT becomes phosphorylated and activated. In turn, activated AKT phosphorylates MDM2, which leads to the nuclear import of MDM2. In the nucleus, MDM2 binds to and degrades p53 (Zhou et al., 2001).