Twist and p53 reciprocally regulate target genes via direct interaction.
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.
Shiota
M
M
Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.
Izumi
H
H
Onitsuka
T
T
Miyamoto
N
N
Kashiwagi
E
E
Kidani
A
A
Hirano
G
G
Takahashi
M
M
Naito
S
S
Kohno
K
K
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
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