Dynamic O-GlcNAcylation coordinates etoposide-triggered tumor cell pyroptosis by regulating p53 stability.

ABSTRACT: O-GlcNAcylation, a modification of nucleocytoplasmic proteins in mammals, plays a critical role in various cellular processes. However, the interplay and their underlying mechanisms in chemotherapy-induced tumor regression between O-GlcNAcylation and pyroptosis, a form of programmed cell death associated with innate immunity, remains unclear. Here, we observed that during the etoposide-induced pyroptosis of SH-SY5Y and A549 cells, overall O-GlcNAcylation levels are substantially reduced. Pharmacological inhibition or genetic manipulation of O-GlcNAcylation, such as OGT inhibition or OGA overexpression, sensitized these cells to etoposide-induced pyroptosis both in vitro and in vivo. Mechanistically, mutations at S96 and S149 residues attenuated p53 O-GlcNAcylation, weakening its interactio

SUBMITTER: Wang J 

PROVIDER: S-EPMC11761933 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature