中国科学院水生生物研究所机构知识库
Advanced  
IHB OpenIR  > 水生生物分子与细胞生物学研究中心  > 期刊论文
题名: Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells
作者: Fan, Huihui1, 2; Cai, Yan2, 4; Xie, Ping2; Xiao, Wuhan3; Chen, Jun2; Ji, Wei3; Zhao, Sujuan2
通讯作者: Xie, P (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China.
关键词: Microcystin-LR ; c-myc ; Protein phosphatase 2A ; Carcinogenicity
刊名: TOXICOLOGY
发表日期: 2014-05-07
DOI: 10.1016/j.tox.2014.02.015
卷: 319, 页:69-74
收录类别: SCI
文章类型: Article
部门归属: [Fan, Huihui] Huazhong Agr Univ, Coll Fisheries, Wuhan, Peoples R China; [Fan, Huihui; Cai, Yan; Xie, Ping; Chen, Jun; Zhao, Sujuan] Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol China, Donghu Expt Stn Lake Ecosyst, Wuhan 430072, Peoples R China; [Xiao, Wuhan; Ji, Wei] Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China; [Cai, Yan] Changzhou Univ, Sch Petrochem Engn, Changzhou, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: National Natural Science Foundation of China [31322013]; State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ07]
类目[WOS]: Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]: Pharmacology & Pharmacy ; Toxicology
摘要: Microcystin-LR is the most toxic and the most frequently encountered toxin produced by the cyanobacteria in the contaminated aquatic environment. Previous studies have demonstrated that Microcystin-LR is a potential carcinogen for animals and humans, and the International Agency for Research on Cancer has classified Microcystin-LR as a possible human carcinogen. However, the precise molecular mechanisms of Microcystin-LR-induced carcinogenesis remain a mystery. C-myc is a proto-oncogene, abnormal expression of which contributes to the tumor development. Although several studies have demonstrated that Microcystin-LR could induce c-myc expression at the transcriptional level, the exact connection between Microcystin-LR toxicity and c-myc response remains unclear. In this study, we showed that the c-myc protein increased in HEK293 cells after exposure to Microcystin-LR. Coexpression of protein phosphatase 2A and two stable c-myc protein point mutants (either c-myc(T58A) or c-myc(562A)) showed that Microcystin-LR increased c-myc protein level mainly through inhibiting protein phosphatase 2A activity which altered the phosphorylation status of serine 62 on c-myc. In addition, we also showed that Microcystin-LR could increase c-myc promoter activity as revealed by luciferase reporter assay. And the TATA box for P1 promoter of c-myc might be involved. Our results suggested that Microcystin-LR can stimulate c-myc transcription and stabilize c-myc protein, which might contribute to hepatic tumorigenesis in animals and humans. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
英文摘要: Microcystin-LR is the most toxic and the most frequently encountered toxin produced by the cyanobacteria in the contaminated aquatic environment. Previous studies have demonstrated that Microcystin-LR is a potential carcinogen for animals and humans, and the International Agency for Research on Cancer has classified Microcystin-LR as a possible human carcinogen. However, the precise molecular mechanisms of Microcystin-LR-induced carcinogenesis remain a mystery. C-myc is a proto-oncogene, abnormal expression of which contributes to the tumor development. Although several studies have demonstrated that Microcystin-LR could induce c-myc expression at the transcriptional level, the exact connection between Microcystin-LR toxicity and c-myc response remains unclear. In this study, we showed that the c-myc protein increased in HEK293 cells after exposure to Microcystin-LR. Coexpression of protein phosphatase 2A and two stable c-myc protein point mutants (either c-myc(T58A) or c-myc(562A)) showed that Microcystin-LR increased c-myc protein level mainly through inhibiting protein phosphatase 2A activity which altered the phosphorylation status of serine 62 on c-myc. In addition, we also showed that Microcystin-LR could increase c-myc promoter activity as revealed by luciferase reporter assay. And the TATA box for P1 promoter of c-myc might be involved. Our results suggested that Microcystin-LR can stimulate c-myc transcription and stabilize c-myc protein, which might contribute to hepatic tumorigenesis in animals and humans. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
关键词[WOS]: CYANOBACTERIAL TOXINS ; PROTEOMIC ANALYSIS ; TUMOR-SUPPRESSOR ; IN-VIVO ; APOPTOSIS ; LIVER ; PHOSPHORYLATION ; TRANSFORMATION ; EXPRESSION ; KIDNEY
语种: 英语
WOS记录号: WOS:000335622400008
ISSN号: 0300-483X
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/20084
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

Files in This Item: Download All
File Name/ File Size Content Type Version Access License
Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells.pdf(1000KB)----开放获取View Download

作者单位: 1.Huazhong Agr Univ, Coll Fisheries, Wuhan, Peoples R China
2.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol China, Donghu Expt Stn Lake Ecosyst, Wuhan 430072, Peoples R China
3.Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China
4.Changzhou Univ, Sch Petrochem Engn, Changzhou, Peoples R China

Recommended Citation:
Fan, Huihui; Cai, Yan; Xie, Ping; Xiao, Wuhan; Chen, Jun; Ji, Wei; Zhao, Sujuan.Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells,TOXICOLOGY,2014,319():69-74
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Fan, Huihui]'s Articles
[Cai, Yan]'s Articles
[Xie, Ping]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Fan, Huihui]‘s Articles
[Cai, Yan]‘s Articles
[Xie, Ping]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
文件名: Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells.pdf
格式: Adobe PDF
此文件暂不支持浏览
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  中国科学院水生生物研究所 - Feedback
Powered by CSpace