Alternatively mechanistic insights into acetylation in p53-mediated transcriptional regulation of cancer cell-intrinsic PD-1.

ABSTRACT: Since the recent discovery of cancer cell-intrinsic programmed cell death protein-1 (PD-1), the mechanisms that manipulate PD-1 functions in tumor development beyond its immune checkpoint roles have become attractive research topics in oncology. Our previous study validated that PD-1 exists in lung cancer cells and is directly transactivated by p53 in a DNA-binding domain (DBD) acetylation-dependent manner. Here, we report that the carboxyl-terminal domain (CTD) of p53 likewise participates in PD-1 transcriptional regulation in cancer cells under different regulatory mechanisms. By mutating the lysine residues within the CTD to mimic either acetylation-deficient or fully acetylated status, we proved that acetylated CTD dramatically impeded p53-mediated transactivation of PD-1. Furthermore,

SUBMITTER: Wen J 

PROVIDER: S-EPMC11197762 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature