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SET mediates TCE-induced liver cell apoptosis through dephosphorylation and upregulation of nucleolin.

ABSTRACT: 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.

SUBMITTER: Ren X

PROVIDER: S-EPMC5522280 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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SET mediates TCE-induced liver cell apoptosis through dephosphorylation and upregulation of nucleolin.

Ren Xiaohu X Huang Xinfeng X Yang Xifei X Liu Yungang Y Liu Wei W Huang Haiyan H Wu Desheng D Zou Fei F Liu Jianjun J

Oncotarget 20170601 25

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, decreas ...[more]

PMID: 28402964

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