title: 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.
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.|School of Public Health, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Ren
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Huang
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.
authors.forename: Xifei
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Public Health, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Yungang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.
authors.forename: Desheng
authors.initials: D
authors.lastname: Wu
authors.affiliation: School of Public Health, Southern Medical University, Guangzhou, 510515, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.affiliation: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins; D055785:Gene Knockdown Techniques; D056488:Histone Chaperones / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D040901:Proteomics; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014241:Trichloroethylene / Q000494:pharmacology*; D015854:Up-Regulation; D000097796:Nucleolin
chemical_list: D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D014241:Trichloroethylene; D000097796:Nucleolin; C513473:SET protein, human
keywords: SET; hepatic cytotoxicity; nucleolin; proteomics; trichloroethylene