2. Academic Validation
  3. Nuclear export of PML promotes p53-mediated apoptosis and ferroptosis

Nuclear export of PML promotes p53-mediated apoptosis and ferroptosis

  • Cell Signal. 2024 Sep:121:111278. doi: 10.1016/j.cellsig.2024.111278.
Yue Ni 1,  Hongce Chen 2,  Qiuqiang Zhan 3,  Zhengfei Zhuang 4
Affiliations

Affiliations

  • 1 MOE Key Laboratory of Laser Life Science & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; Centre for Optical and Electromagnetic Research, South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou 510631, China.
  • 2 MOE Key Laboratory of Laser Life Science & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. Electronic address: chenhce@m.scnu.edu.cn.
  • 3 Centre for Optical and Electromagnetic Research, South China Academy of Advanced Optoelectronics, South China Normal University, Guangzhou 510631, China.
  • 4 MOE Key Laboratory of Laser Life Science & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. Electronic address: zhuangzf@scnu.edu.cn.
PMID: 38944257 DOI: 10.1016/j.cellsig.2024.111278
Abstract

Promyelocytic leukemia protein (PML), a tumor suppressor protein, plays a key role in cell cycle regulation, Apoptosis, senescence and cellular metabolism. Here, we report that PML promotes Apoptosis and Ferroptosis. Our data showed that PML over-expression inhibited cell proliferation and migration. PML over-expression increased apoptotic cells, nuclear condensation and the loss of mitochondrial membrane potential, accompanied by regulation of Bcl-2 Family proteins and Reactive Oxygen Species (ROS) level, suggesting that PML enhanced Apoptosis. Meanwhile, PML over-expression not only increased lipid ROS accumulation and Malondialdehyde (MDA) content but also downregulated solute carrier family 7 member 11 (SLC7A11) and Glutathione Peroxidase 4 (GPX4) expression, indicating that PML enhanced Ferroptosis. Additionally, knockdown of p53 attenuated the effect of PML on SLC7A11 and GPX4, and inhibited the increase of lipid ROS and ROS by PML over-expression. Moreover, translocation of PML from nucleus to cytoplasm not only promoted Apoptosis and Ferroptosis, but also inhibited cell proliferation. Taken together, PML promotes Apoptosis and Ferroptosis, in which the mediation of p53 and the nuclear export of PML play important roles.

Keywords

Apoptosis; Ferroptosis; Nuclear export; PML; p53.

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