SET mediates TCE-induced liver cell apoptosis through dephosphorylation and upregulation of nucleolin
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Xiaohu Ren1,2, Xinfeng Huang1, Xifei Yang1, Yungang Liu2, Wei Liu1, Haiyan Huang1, Desheng Wu1, Fei Zou2 and Jianjun Liu1
1Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China
2School of Public Health, Southern Medical University, Guangzhou, 510515, China
Jianjun Liu, email: [email protected], [email protected]
Fei Zou, email: [email protected]
Keywords: trichloroethylene, nucleolin, SET, hepatic cytotoxicity, proteomics
Received: August 26, 2016 Accepted: February 12, 2017 Published: April 03, 2017
Trichloroethylene (TCE) is an occupational and environmental chemical that can cause severe hepatotoxicity. While our previous studies showed that the phosphatase inhibitor SET is a key mediator of TCE-induced liver cell apoptosis, the molecular mechanisms remain elusive. Using quantitative phosphoproteomic analysis, we report here that nucleolin is a SET-regulated phosphoprotein in human liver HL-7702 cells. Functional analysis suggested that SET promoted dephosphorylation of nucleolin, decreased its binding to its transcriptional activator, c-myc, and upregulated nucleolin expression in TCE-treated cells. Importantly, TCE-induced hepatocyte apoptosis was significantly attenuated when nucleolin was downregulated with specific siRNAs. These findings indicate that TCE may induce hepatocyte apoptosis via SET-mediated dephosphorylation and overexpression of nucleolin.
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