Journal
FEBS LETTERS
Volume 584, Issue 11, Pages 2291-2297Publisher
WILEY
DOI: 10.1016/j.febslet.2010.03.040
Keywords
Manganese superoxide dismutase; Reactive oxygen species; Extracellular regulated kinase; Nuclear translocation; p53
Funding
- National Natural Science Foundation of China [30770491, 30970655]
- Natural Science Foundation of Beijing [5082015, 7032034]
- State Key Laboratory Special Fund [2060204]
- Ministry of Education, China [20091106110025]
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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. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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