Figure 3.

The crosstalk between ATM/MDM2/p53 and PTEN/PI3K/AKT pathways under the exposure to genotoxic and metabolic stressor. ATM kinase undergoes activation upon genotoxic stressor occurrence. It conducts MDM2 Ser395 phosphorylation as well as phosphorylating p53 at Ser15. MDM2 cannot negatively regulate p53, which immediately gets stabilized and accumulates. Positive regulation of p53 is performed due to its deubiquitination by activated USP10. Nuclear p53 tetramerization allows for transcriptional regulation of genes involved in provision of antioncogenic cellular protection. PTEN is one of the p53 target genes responsible for the inhibition of insulin signalling. In addition to the blockage of phospho-AKT formation, p53 triggers AKT proteosomal degradation. p53 translation is enhanced by the formation of p53mRNA-MDM2 complex and inhibited RPL26 degradation. While blue lines depict phenomena present upon stressor occurrence, red lines represent inhibited signalling events. RE stands for response element. Only limited number of regulatory events is shown.