Nucleophosmin Regulates Intracellular Oxidative Stress Homeostasis via Antioxidant PRDX6

ABSTRACT 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 regula...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2017-12, Vol.118 (12), p.4697-4707
Main Authors: Liu, Guo‐Yan, Shi, Jing‐Xian, Shi, Song‐Lin, Liu, Fan, Rui, Gang, Li, Xiao, Gao, Li‐Bin, Deng, Xiao‐Ling, Li, Qi‐Fu
Format: Article
Language:English
Subjects:
Antioxidants
Antioxidants - metabolism
Cancer
Cell Line, Tumor
Cytoplasm
Gene expression
Hematology
Homeostasis
Humans
Immunoprecipitation
Indoles - pharmacology
INTERACTIONAL PROTEIN NETWORK
Localization
Mutation
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
NUCLEOPHOSMIN
Oligomerization
Overexpression
Oxidative Stress
Peroxiredoxin
PEROXIREDOXIN 6
Peroxiredoxin VI - antagonists & inhibitors
Peroxiredoxin VI - genetics
Peroxiredoxin VI - metabolism
Proteins
PROTEOMICS
REACTIVE OXYGEN SPECIES
Reactive Oxygen Species - metabolism
Regulatory mechanisms (biology)
Relocation
Solid tumors
Tumor cells
Tumors
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Summary:ABSTRACT 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.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.26135