Twist and p53 reciprocally regulate target genes via direct interaction
Twist and p53 reciprocally regulate target genes via direct interaction
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DOI：
10.1038/onc.2008.176
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发表时间：
2008-09-18
期刊：
影响因子：
8
通讯作者：
Kohno, K.
中科院分区：
文献类型：
--
作者：
Shiota, M.;Izumi, H.;Kohno, K.
Twist是一种基本的螺旋-环-螺旋转录因子，与基因启动子中的E盒结合。Twist通过干扰p53的肿瘤抑制功能而具有致癌功能。使用膜下拉试验，我们发现，扭曲直接与p53相互作用，这种相互作用的基础上的p53靶基因表达的抑制作用。Twist与p53的DNA结合结构域相互作用并抑制p53的DNA结合活性。Twist的表达显著抑制了p53对p21启动子的转录激活。另一方面，p53与Twist的N-末端结构域相互作用并抑制Twist依赖的YB-1启动子活性。重要的是，我们发现，p53依赖的生长抑制被Twist或YB-1的表达所取消。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。
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.