The regulation of CP-31398 on liquid-liquid phase separation of p53

Abstract

The tumor suppressor p53 could regulate the cell cycle arrest, DNA repair and apoptosis. It underwent liquid-liquid phase separation (LLPS) to form droplets. CP-31398 was thought as the activator of p53. In this work, the regulation of CP-31398 on the LLPS of p53 was investigated. The results revealed that CP-31398 promoted the LLPS of p53, delayed the solidification of p53 droplets and increased the mobility of p53 droplets. It also enhanced the tolerance of p53 droplets to the negative charges, and improved the phase behavior of heterotypic p53-pol II CTD droplets. The p53-CP-31398 droplets were driven by hydrogen bonds, hydrophobic and electrostatic interactions. These findings clarified that CP-31398 could elevate the transcriptional function of p53 probably by modulating the phase behavior. The study provided new insights into the regulation mechanism of p53 and potential therapeutic avenues for cancer.