Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.
Oncogene. 2008 Sep 18;27(42):5543-53. doi: 10.1038/onc.2008.176. Epub 2008 May 26.
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.
Twist 是一种基本的螺旋-环-螺旋转录因子，可与基因启动子中的 E 盒结合。 Twist 通过干扰 p53 的肿瘤抑制功能发挥致癌作用。通过膜下拉测定，我们发现 Twist 可直接与 p53 相互作用，这种相互作用是抑制 p53 靶基因表达的基础。 Twist 与 p53 的 DNA 结合域相互作用并抑制 p53 的 DNA 结合活性。p53 通过转录激活 p21 启动子，而 Twist 的表达则显著抑制了 p53 的转录激活活性。另一方面，p53 与 Twist 的 N 端结构域相互作用并抑制 Twist 依赖性 YB-1 启动子活性。重要的是，我们发现表达 Twist 或 YB-1 会取消 p53 依赖性的生长抑制作用。因此，我们的数据表明 Twist 通过与 p53 的直接相互作用抑制 p53 功能。
