Current advances in the inhibition of the auto-regulatory interaction between the p53 tumour suppressor protein and MDM2 protein

The p53 tumour suppressor protein is involved in co-ordinating the cellular response to genotoxic stress through initiating a G1-growth arrest and/or induction of apoptosis and thereby influences the success of most anticancer treatments. p53 is a damage-inducible transcription factor whose activity is negatively regulated by the binding of MDM2 protein. The ability to disrupt the p53-MDM2 regulatory loop has identified a novel therapeutic opportunity. Potent peptide inhibitors of the interaction between p53 and MDM2 protein have been identified, with IC50 values in the nanomolar range, and activate the p53-dependent stress response. Potentially, such peptides might have a wider application as non-genotoxic therapeutic p53 activators, in tumours that retain expression of wild type p53 protein, to induce the p53-dependent apoptotic pathway