P53 transcription-independent activity mediates selenite-induced acute promyelocytic leukemia NB4 cell apoptosis.
Selenium, an essential trace element possessing anti-carcinogenic properties, can induce apoptosis in cancer cells. We have previously shown that sodium selenite can induce apoptosis by activating the mitochondrial apoptosis pathway in NB4 cells. However, the detailed mechanism remains unclear. Presently, we demonstrate that p53 contributes to apoptosis by directing signaling at the mitochondria. Immunofluorescent and Western blot procedures revealed selenite-induced p53 translocation to mitochondria. Inhibition of p53 blocked accumulation of reactive oxygen species (ROS) and loss of mitochondrial membrane potential, suggesting that mitochondrial p53 acts as an upstream signal of ROS and activates the mitochondrial apoptosis pathway. Selenite also disrupted cellular calcium ion homeostasis in a ROS-dependent manner and increased mitochondrial calcium ion concentration. p38 kinase mediated phosphorylation and mitochondrial translocation of p53. Taken together, these results indicate that p53 involves selenite-induced NB4 cell apoptosis by translocation to mitochondria and activation mitochondrial apoptosis pathway in a transcription-independent manner.
Guan
Liying
L
National Laboratory of Medical Molecular Biology, Institute of Basic Medicine Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Huang
Fang
F
Li
Zhushi
Z
Han
Bingshe
B
Jiang
Qian
Q
Ren
Yun
Y
Yang
Yang
Y
Xu
Caimin
C
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D018038:Sodium Selenite / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D010768:Phosphoserine; D048051:p38 Mitogen-Activated Protein Kinases; D018038:Sodium Selenite; D002118:Calcium