p53 Basic C Terminus Regulates p53 Functions through DNA Binding Modulation of Subset of Target Genes
p53 Basic C Terminus Regulates p53 Functions through DNA Binding Modulation of Subset of Target Genes
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DOI：
10.1074/jbc.m111.331298
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发表时间：
2012-06-22
影响因子：
4.8
通讯作者：
Manfredi, James J.
中科院分区：
文献类型：
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作者：
Hamard, Pierre-Jacques;Lukin, Dana J.;Manfredi, James J.
p53基因编码的转录因子由几个功能结构域组成：N-末端反式激活结构域、中央序列特异性DNA结合结构域、四聚化结构域和高度碱性的C-末端调节结构域（CTD）。p53 CTD是一种非特异性DNA结合结构域，可进行广泛的翻译后修饰。然而，p53 CTD的功能意义仍不清楚。通过比较异位表达的野生型（WT）p53蛋白与缺乏24个末端氨基酸（Delta 24）的截短突变体的活性，探索了该结构域在p53功能调节中的作用。使用定量真实的时间PCR和染色质免疫沉淀实验，显示p53 CTD缺失由于受损的特异性DNA结合而改变其靶基因子集的p53依赖性诱导。此外，p53诱导的生长停滞和凋亡都需要完整的p53 CTD。这些数据表明p53 CTD是p53肿瘤抑制功能的正调节因子。
The p53 gene encodes a transcription factor that is composed of several functional domains: the N-terminal transactivation domain, the central sequence-specific DNA binding domain, the tetramerization domain, and the highly basic C-terminal regulatory domain (CTD). The p53 CTD is a nonspecific DNA binding domain that is subject to extensive post-translational modifications. However, the functional significance of the p53 CTD remains unclear. The role of this domain in the regulation of p53 functions is explored by comparing the activity of ectopically expressed wild-type (WT) p53 protein to that of a truncated mutant lacking the 24 terminal amino acids (Delta 24). Using quantitative real time PCR and chromatin Immuno-Precipitation experiments, a p53 CTD deletion is shown to alter the p53-dependent induction of a subset of its target genes due to impaired specific DNA binding. Moreover, p53-induced growth arrest and apoptosis both require an intact p53 CTD. These data indicate that the p53 CTD is a positive regulator of p53 tumor suppressor functions.