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Author Li, Lingzhi ♦ Qiu, Ping ♦ Chen, Bailing ♦ Lu, Yongju ♦ Wu, Kai ♦ Thakur, Chitra ♦ Chang, Qingshan ♦ Sun, Jiaying ♦ Chen, Fei
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ANTIOXIDANTS ♦ ARSENIC ♦ ARSENIC IONS ♦ CYSTEINE ♦ CYTOPLASM ♦ HYDROGEN PEROXIDE ♦ INHIBITION ♦ INTERACTIONS ♦ LUNGS ♦ NEOPLASMS ♦ NUCLEI ♦ OXIDATION ♦ OXYGEN ♦ PHOSPHORYLATION ♦ PROTEINS ♦ SERINE ♦ SIGNALS ♦ STRESSES ♦ TRANSLOCATION
Abstract Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H{sub 2}O{sub 2}, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H{sub 2}O{sub 2}. Furthermore, both arsenic and H{sub 2}O{sub 2} were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As{sup 3+}) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As{sup 3+}-induced EZH2 phosphorylation. • As{sup 3+} induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2014-05-01
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 276
Issue Number 3


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