3 years ago

Nucleophosmin Regulates Intracellular Oxidative Stress Homeostasis via Antioxidant PRDX6

Nucleophosmin Regulates Intracellular Oxidative Stress Homeostasis via Antioxidant PRDX6
Guo-Yan Liu, Li-Bin Gao, Xiao Li, Jing-Xian Shi, Qi-Fu Li, Gang Rui, Song-Lin Shi, Fan Liu, Xiao-Ling Deng
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. Reactive oxygen species (ROS) play both as a deleterious and beneficial species in cancer cells. Our results demonstrated that NPM, a nucleolar phosphorylated protein heavily implicated in cancers of diverse origins, affected the homeostatic balance of oxidative stress in tumor cells via PRDX6 protein. The regulation axis of NPM/PRDX6/ROS may provide a novel therapeutic target for cancer treatment.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jcb.26135

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