Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells

CORC > 水生生物研究所 > 中科院水生所知识产出（2009年前） > 水生生物分子与细胞生物学研究中心 > 期刊论文

	Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells
	Fan, Huihui 1,2; Cai, Yan 2,4; Xie, Ping 2; Xiao, Wuhan 3; Chen, Jun 2; Ji, Wei 3; Zhao, Sujuan 2
刊名	TOXICOLOGY
	2014-05-07
卷号	319 页码:69-74
关键词	Microcystin-LR c-myc Protein phosphatase 2A Carcinogenicity
ISSN号	0300-483X
通讯作者	Xie, P (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China.
中文摘要	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.
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.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]	Pharmacology & Pharmacy ; Toxicology
关键词[WOS]	CYANOBACTERIAL TOXINS ; PROTEOMIC ANALYSIS ; TUMOR-SUPPRESSOR ; IN-VIVO ; APOPTOSIS ; LIVER ; PHOSPHORYLATION ; TRANSFORMATION ; EXPRESSION ; KIDNEY
收录类别	SCI
资助信息	National Natural Science Foundation of China [31322013]; State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ07]
语种	英语
WOS记录号	WOS:000335622400008
公开日期	2014-08-13
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/20084]
专题	水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文
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
推荐引用方式 GB/T 7714	Fan, Huihui,Cai, Yan,Xie, Ping,et al. Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells[J]. TOXICOLOGY,2014,319:69-74.
APA	Fan, Huihui.,Cai, Yan.,Xie, Ping.,Xiao, Wuhan.,Chen, Jun.,...&Zhao, Sujuan.(2014).Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells.TOXICOLOGY,319,69-74.
MLA	Fan, Huihui,et al."Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells".TOXICOLOGY 319(2014):69-74.