ROS leads to MnSOD upregulation through ERK2 translocation and p53 activation in selenite-induced apoptosis of NB4 cells.
Following our previous finding that sodium selenite induces apoptosis in human leukemia NB4 cells, we now show that the expression of the critical antioxidant enzyme manganese superoxide dismutase (MnSOD) is remarkably elevated during this process. We further reveal that reactive oxygen species (ROS), especially superoxide radicals, play a crucial role in selenite-induced MnSOD upregulation, with extracellular regulated kinase (ERK) and p53 closely implicated. Specifically, ERK2 translocates into the nucleus driven by ROS, where it directly phosphorylates p53, leading to dissociation of p53 from its inhibitory protein mouse double minute 2 (MDM2). Active p53 directly mediates the expression of MnSOD, serving as the link between ERK2 translocation and MnSOD upregulation.
Li
Zhushi
Z
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Shi
Kejian
K
Guan
Liying
L
Cao
Tingming
T
Jiang
Qian
Q
Yang
Yang
Y
Xu
Caimin
C
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D016158:Genes, p53; D006801:Humans; D021381:Protein Transport / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018038:Sodium Selenite / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D013481:Superoxides; D013482:Superoxide Dismutase; D018038:Sodium Selenite