Figure 2.

The crosstalk between MDM2/p53 and PI3K/AKT pathways under physiological conditions. Insulin signalling triggers cellular growth and survival. Activated AKT performs MDM2 Ser166 and 186 phosphorylation thereby allowing for the degradation of p53 in the cytoplasm and nucleus. Thus, p53 cannot transcriptionally regulate the plethora of target genes, where these enabling cell cycle arrest, senescence, and apoptosis are of crucial importance. Blue lines denote molecular mechanisms present under physiological conditions. RE stands for response element. See the text for more details.