期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 118, 期 12, 页码 4697-4707出版社
WILEY
DOI: 10.1002/jcb.26135
关键词
NUCLEOPHOSMIN; REACTIVE OXYGEN SPECIES; PEROXIREDOXIN 6; INTERACTIONAL PROTEIN NETWORK; PROTEOMICS
资金
- National Natural Science Foundation of China [81272245, 81670542, 81272921, 81272445, 81471970]
- Joint Programme by Healthy Care System and Educational Department in Fujian Province [WKJ-FJ-16]
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. (c) 2017 Wiley Periodicals, Inc.
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