This interaction relies heavily on specific residues, namely Phe19, Trp23, and Leu26, identified using the p53–MDM2 crystal structure (PDB: 1YCR).4 The key residues are arranged on a single face of the α-helix of p53 and make a substantial contribution to the binding energy (Fig. 1).4 The identification of the p53 sequence that interacts with MDM2 has facilitated the development of small molecules and peptides aimed at disrupting the p53–MDM2 PPI as a strategy to restore p53-dependent tumour suppressor activity in cancers. This evidence concerns the gene TP53 and neoplasm.