title: Apoptin selectively induces the apoptosis of tumor cells by suppressing the transcription of HSP70.
abstract: Apoptin is a nonstructural viral protein encoded by VP3 gene of chicken anemia virus, which could specially induce apoptosis of tumor cells. However, the mechanism of apoptin-induced apoptosis in tumor cells without any side effects in normal cells has not yet been well characterized. This study aimed to investigate the molecular mechanism underlying the selective antitumor effects of apoptin. HepG2 cells were treated with apoptin or transfected with apoptin expression vector. Heat shock protein 70 (HSP70) expression was examined by Western blot. The binding of apoptin to HSP70 promoter was detected by electrophoretic mobility shift assay, chromatin immunoprecipitation, and luciferase assay. The results showed that apoptin inhibited HSP70 expression in HepG2 cells and apoptin-induced apoptosis of HepG2 cells was dependent on the expression level of HSP70. Furthermore, apoptin promoted HSF1 trimer depolymerization and inhibited HSF1-mediated HSP70 transcription. In addition, apoptin competed with HSF1 to bind heat shock element in HSP70 promoter, leading to reduced HSP70 transcription. Both these mechanisms contribute to the suppression of HSP70 transcription and expression. Our findings provide the first evidence that apoptin induces tumor cell apoptosis by specifically downregulating the expression of HSP70, which helps explain the specific antitumor effects of apoptin.
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Daqing Campus, Daqing, 163319, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Yuan
authors.forename: Liqiu
authors.initials: L
authors.lastname: Zhang
authors.forename: Xingli
authors.initials: X
authors.lastname: Dong
authors.forename: Hengyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Shuyan
authors.initials: S
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.forename: Xinghan
authors.initials: X
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D036022:Capsid Proteins / Q000378:metabolism* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D000076249:Heat Shock Transcription Factors; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms; D011401:Promoter Regions, Genetic; D055503:Protein Multimerization / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D036022:Capsid Proteins; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; C091717:VP3 protein, Chicken anemia virus