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Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells
Fan, Huihui1,2; Cai, Yan2,4; Xie, Ping2; Xiao, Wuhan3; Chen, Jun2; Ji, Wei3; Zhao, Sujuan2; Xie, P (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China.
2014-05-07
Source PublicationTOXICOLOGY
ISSN0300-483X
Volume319Pages:69-74
AbstractMicrocystin-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.; 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.
SubtypeArticle
KeywordMicrocystin-lr C-myc Protein Phosphatase 2a Carcinogenicity
Department[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
DOI10.1016/j.tox.2014.02.015
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationNational Natural Science Foundation of China [31322013]; State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ07] ; National Natural Science Foundation of China [31322013]; State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ07] ; National Natural Science Foundation of China [31322013]; State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ07] ; National Natural Science Foundation of China [31322013]; State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ07]
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy ; Toxicology
WOS SubjectPharmacology & Pharmacy ; Toxicology
WOS IDWOS:000335622400008
WOS KeywordCYANOBACTERIAL TOXINS ; PROTEOMIC ANALYSIS ; TUMOR-SUPPRESSOR ; IN-VIVO ; APOPTOSIS ; LIVER ; PHOSPHORYLATION ; TRANSFORMATION ; EXPRESSION ; KIDNEY
Funding OrganizationNational Natural Science Foundation of China [31322013]; State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ07] ; National Natural Science Foundation of China [31322013]; State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ07] ; National Natural Science Foundation of China [31322013]; State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ07] ; National Natural Science Foundation of China [31322013]; State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ07]
Citation statistics
Cited Times:16[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/20084
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorXie, P (reprint author), Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Peoples R China.
Affiliation1.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
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.,...&Xie, P .(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.
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