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Nucleophosmin Regulates Intracellular Oxidative Stress Homeostasis via Antioxidant PRDX6
Author(s) -
Liu GuoYan,
Shi JingXian,
Shi SongLin,
Liu Fan,
Rui Gang,
Li Xiao,
Gao LiBin,
Deng XiaoLing,
Li QiFu
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26135
Subject(s) - nucleophosmin , peroxiredoxin , gene knockdown , oxidative stress , downregulation and upregulation , reactive oxygen species , microbiology and biotechnology , biology , subcellular localization , cytoplasm , chemistry , cancer research , apoptosis , biochemistry , gene , enzyme , peroxidase , myeloid leukemia
Reactive oxygen species (ROS) play both deleterious and beneficial roles in cancer cells. Nucleophosmin (NPM) is heavily implicated in cancers of diverse origins, being its gene over‐expression in solid tumors or frequent mutations in hematological malignancies. However, the role and regulatory mechanism of NPM in oxidative stress are unclear. Here, we found that NPM regulated the expression of peroxiredoxin 6 (PRDX6), a member of thiol‐specific antioxidant protein family, consequently affected the level and distribution of ROS. Our data indicated that NPM knockdown caused the increase of ROS and its relocation from cytoplasm to nucleoplasm. In contrast, overexpression or cytoplasmic localization of NPM upregulated PRDX6, and decreased ROS. In addition, NPM knockdown decreased peroxiredoxin family proteins, including PRDX1, PRDX4, and PRDX6. Co‐immunoprecipitation further confirmed the interaction between PRDX6 and NPM. Moreover, NSC348884, an inhibitor specifically targeting NPM oligomerization, decreased PRDX6 and significantly upregulated ROS. These observations demonstrated that the expression and localization of NPM affected the homeostatic balance of oxidative stress in tumor cells via PRDX6 protein. The regulation axis of NPM/PRDX/ROS may provide a novel therapeutic target for cancer treatment. J. Cell. Biochem. 118: 4697–4707, 2017. © 2017 Wiley Periodicals, Inc.