G3BP1 介导的 P53 核定位对急性肝衰竭中铁死亡的影响。

Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.

Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, China.

Apoptosis. 2023 Aug;28(7-8):1226-1240. doi: 10.1007/s10495-023-01856-y. Epub 2023 May 27.

This study investigated whether G3BP1 could regulate ferroptosis in hepatocytes during ALF by affecting the entry of P53 into the nucleus. Promoting G3BP1 expression could inhibit P53 entry by binding to the nuclear localization sequence of P53. The inhibition of SLC7A11 transcription was weakened after blocking of P53 binding to the promoter region of the SLC7A11 gene. The SLC7A11-GSH-GPX4 antiferroptotic pathway was subsequently activated, and the level of ferroptosis in ALF hepatocytes was inhibited.

本研究通过影响 P53 进入细胞核来研究 G3BP1 是否可以通过影响 P53 进入细胞核来调节 ALF 期间肝细胞中的铁死亡。促进 G3BP1 表达可以通过与 P53 的核定位序列结合来抑制 P53 进入细胞核。阻断 P53 与 SLC7A11 基因启动子区域结合后，SLC7A11 转录的抑制作用减弱。随后激活 SLC7A11-GSH-GPX4 抗铁死亡途径，抑制 ALF 肝细胞中的铁死亡水平。