title: Characterization of the 5'-flanking region of the human TP53 gene and its response to the natural compound, Resveratrol.
abstract: Tumour suppressor p53, which is encoded by theTP53gene, is widely known to play an important role in response to DNA damage and various stresses. It has recently been reported that p53 regulates glucose metabolism and that an increase in p53 protein level is induced after serum deprivation or treatments with a natural compound,trans-Resveratrol (Rsv). In this study, we constructed a Luciferase expression vector, pGL4-TP53-551, containing 551 bp of the 5'-upstream region of the humanTP53gene, which was then transfected into HeLa S3 cells. A Luciferase assay showed that Rsv treatment increased the promoter activity of theTP53gene in comparison to that ofPIF1 Detailed deletion and mutation analyses revealed that Nkx-2.5 and E2F-binding elements are required in addition to duplicated GGAA (TTCC), for the regulation ofTP53promoter activity. In this study, it is suggested that the transient induction ofTP53gene expression by Rsv treatment might be partly involved in its anti-aging effect through maintenance of chromosomal DNAs.
authors.affiliation: Department of Gene Regulation, Faculty of Pharmaceutical Sciences; Research Center for RNA Science, RIST; uchiumi@rs.noda.tus.ac.jp.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Uchiumi
authors.affiliation: Department of Gene Regulation, Faculty of Pharmaceutical Sciences;
authors.forename: Koichiro
authors.initials: K
authors.lastname: Shoji
authors.affiliation: Department of Gene Regulation, Faculty of Pharmaceutical Sciences;
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Gene Regulation, Faculty of Pharmaceutical Sciences;
authors.forename: Moe
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Gene Regulation, Faculty of Pharmaceutical Sciences;
authors.forename: Yamato
authors.initials: Y
authors.lastname: Sasaki
authors.affiliation: Department of Gene Regulation, Faculty of Pharmaceutical Sciences;
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Department of Gene Regulation, Faculty of Pharmaceutical Sciences;
authors.forename: Kyoko
authors.initials: K
authors.lastname: Sugisawa
authors.affiliation: Research Center for RNA Science, RIST; Biochemistry, Faculty of Pharmaceutical Sciences; and Drug Creation Frontier Research Center, RIST, Tokyo University of Science, Noda-shi, Chiba-ken 278-8510, Japan.
authors.forename: Sei-ichi
authors.initials: S
authors.lastname: Tanuma
mesh_terms: D024506:5' Flanking Region; D000975:Antioxidants / Q000494:pharmacology*; D001665:Binding Sites / Q000235:genetics; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics; D004265:DNA Helicases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D009154:Mutation; D011401:Promoter Regions, Genetic; D000077185:Resveratrol; D017384:Sequence Deletion; D013267:Stilbenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000975:Antioxidants; D013267:Stilbenes; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D008156:Luciferases; D004265:DNA Helicases; C508765:PIF1 protein, human; D000077185:Resveratrol
keywords: E2F; ETS; Nkx-2.5; Resveratrol; TP53