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.
Mesh Terms:
Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, DNA, DNA-Binding Proteins, Gene Expression Regulation, Humans, Nuclear Proteins, Promoter Regions, Genetic, Tumor Suppressor Protein p53, Twist Transcription Factor, Y-Box-Binding Protein 1
Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, DNA, DNA-Binding Proteins, Gene Expression Regulation, Humans, Nuclear Proteins, Promoter Regions, Genetic, Tumor Suppressor Protein p53, Twist Transcription Factor, Y-Box-Binding Protein 1
Oncogene
Date: Sep. 18, 2008
PubMed ID: 18504427
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