p53 – the most frequently mutated protein in human cancer – regulates an array of genes involved in numerous cellular processes, so p53 activity needs highly specific regulation. For example, the selection of p53 target genes is controlled by protein partners, including an inhibitor called iASPP. Now, a team working with Xin Lu at Ludwig Oxford and Yvonne Jones at STRUBI have identified a DNA signature for genes co-regulated by iASPP and p53, and have worked out precisely how iASPP interacts with p53. Surprisingly, their protein structure, published in the journal PNAS, shows that iASPP contacts a different part of p53 to that used by other p53 cellular partners. Instead, the iASPP interaction surface overlaps the site used by a cancer-causing protein from human papillomavirus (HPV). This work could open new prospects for designing anticancer agents targeting p53.
Tuning a tumour suppressor
12 August 2019
New research from Xin Lu’s group shows how a partner of the tumour suppressor p53 mediates target gene selection.