Regulation of p53 Activity by Reversible-Acetylation in Prostate Tumor Suppression

摘要

The importance of p53 on prostate cancer is underlined by clinical observations that p53 alteration can be seen in most metastatic prostate cancers. The finding that re-introduction of wild-type p53 can cause growth arrest of prostate cancer cells further support the role of p53 in prostate tumor suppression. Therefore, to study on prostate tumor development and a therapeutic strategy targeting p53, it is necessary to understand how p53 is activated. To study this, we focus the p53 acetylation, which has been found as a potential mechanism of p53 activation, and investigate how acetylation controls the activity of p53. In this report, we provide the evidence that acetylation regulates p53 subcellular localization. Our study identifies acetylation as a novel mechanism that regulates p53 nucleus-cytoplasm trafficking by neutralizing C-terminal lysine residues, which in turn, controls the oligomerization dependent nuclear export machinery. Although further investigations are needed to address the significance of acetylation-induced p53 trafficking in prostate cancer, our findings provide the basis for a more powerful therapy for prostate tumor suppression.