title: Twist and p53 reciprocally regulate target genes via direct interaction.
abstract: Twist is basic helix-loop-helix transcription factor that binds to E-boxes in gene promoters. Twist possesses an oncogenic function by interfering with the tumor suppressor function of p53. Using a membrane pull-down assay, we found that Twist directly interacts with p53 and that this interaction underlies the inhibitory effects on p53 target gene expression. Twist interacted with the DNA-binding domain of p53 and suppressed the DNA-binding activity of p53. Transcriptional activation of the p21 promoter by p53 was significantly repressed by the expression of Twist. On the other hand, p53 interacted with the N-terminal domain of Twist and repressed Twist-dependent YB-1 promoter activity. Importantly, we found that p53-dependent growth suppression was canceled by the expression of either Twist or YB-1. Thus, our data suggest that Twist inhibits p53 function via a direct interaction with p53.
authors.affiliation: Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shiota
authors.forename: H
authors.initials: H
authors.lastname: Izumi
authors.forename: T
authors.initials: T
authors.lastname: Onitsuka
authors.forename: N
authors.initials: N
authors.lastname: Miyamoto
authors.forename: E
authors.initials: E
authors.lastname: Kashiwagi
authors.forename: A
authors.initials: A
authors.lastname: Kidani
authors.forename: G
authors.initials: G
authors.lastname: Hirano
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Naito
authors.forename: K
authors.initials: K
authors.lastname: Kohno
mesh_terms: D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D051879:Twist-Related Protein 1 / Q000502:physiology*; D051840:Y-Box-Binding Protein 1
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D016159:Tumor Suppressor Protein p53; D051879:Twist-Related Protein 1; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D004247:DNA