Deciphering a molecular tug-of-war in cancer using semisynthetic proteins

The tumor suppressor protein p53 plays a central role in preventing cancer. Post-translational modifications (PTMs) control p53’s anticancer response. Conversely, p53 is inactivated in most cancers, either by mutagenesis or through the expression of viral oncoproteins. How viral suppressors of p53 and activating PTMs vie for control over p53 signalling is poorly understood. This project leverages our expertise in protein semisynthesis to investigate p53 signalling in HPV positive head-and-neck cancers and explores the possibility whether jump-starting p53 through activating PTMs and inhibition of degradation can rescue the anticancer activity of p53 in these cells.