title: Unexpected heat shock element binding ability and tumor-killing activity of the combinatorial function domain of apoptin.
abstract: Apoptin, derived from the chicken anemia virus, has been found to exert tumor-preferential apoptotic activity. It is a potential anticancer agent with direct clinical applications. However, if this viral protein were to be used as a new drug, it might also induce a strong immune response, causing toxic side effects. In a previous study, our group showed that TAT-apoptin downregulates the stress expression of heat shock protein 70 by competing with heat shock factor protein 1 in binding to the heat shock element (HSE) of the promoter region of heat shock protein 70, thus inducing specific apoptosis in HepG2 cells. In this study, we investigated the HSE-binding properties of the minimal functional region of apoptin. We showed that apoptin's nuclear localization signals 1 and nuclear localization signals 2 represented functional regions that could bind with HSE and that this binding capacity was increased by polymers formed through the introduction of a leucine-rich stretch. Our data also showed that truncated combinatorial apoptin peptide has greater tumor-specific cell-killing activity and could be a potential antitumor agent.
authors.affiliation: aDepartment of Parasitology bDepartment of Pharmacology cDepartment of Biopharmaceutical Sciences, College of Pharmacy dTeaching Experiment Center of Biotechnology, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Liqiu
authors.initials: L
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.forename: Weiwei
authors.initials: W
authors.lastname: Song
authors.forename: Hong
authors.initials: H
authors.lastname: Ling
authors.forename: Xingli
authors.initials: X
authors.lastname: Dong
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D036022:Capsid Proteins / Q000378:metabolism* / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000076249:Heat Shock Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D000072417:Protein Domains; D023041:Xenograft Model Antitumor Assays
chemical_list: D036022:Capsid Proteins; D004273:DNA, Neoplasm; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D010446:Peptide Fragments; C091717:VP3 protein, Chicken anemia virus