Tuning a tumor suppressor

New research from Ludwig Oxford’s Xin Lu’s group shows how a partner of the tumor suppressor p52 mediates target gene selection

August 12, 2019 – 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 Ludwig Oxford Director Xin Lu and Yvonne Jones at the University of Oxford 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.



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