Dual regulation of the ΔNp63 transcriptional activity by ΔNp63 in human nasopharyngeal carcinoma cell
Dual regulation of the ΔNp63 transcriptional activity by ΔNp63 in human nasopharyngeal carcinoma cell
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DOI：
10.1016/j.bbrc.2006.02.111
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发表时间：
2006-04-21
影响因子：
3.1
通讯作者：
Chen, JK
中科院分区：
文献类型：
--
作者：
Chu, WK;Lee, KC;Chen, JK
缺乏nh2末端反激活域的p63剪接变异体，即Delta Np63，被认为可以拮抗p53和p63的功能，并被认为在角质形成细胞分化中发挥作用。在这里，我们发现Delta Np63对NPC-076细胞中其自身启动子的活性具有双重调节作用。当Delta Np63低水平存在时，观察到转录活性下调。相反，当Delta Np63高水平表达时，可以观察到Delta Np63转录活性的上调。当Delta Np63启动子的p53结合位点发生突变时，下调作用被取消。与之形成鲜明对比的是，在相同的实验条件下，相似的突变并不影响Delta Np63转录活性的上调。进一步的研究表明，这种上调与STAT3的激活有关，因为STAT3核易位的阻断消除了Delta Np63的上调。因此，Delta Np63在NPC-076细胞中双向调控Delta Np63的转录活性。(c) 2006爱思唯尔公司版权所有。
p63 splicing variants lacking NH2-terminal transactivating domain, known as Delta Np63, are thought to antagonize p53 and p63 functions and are suggested to play roles in keratinocyte differentiation. Here, we show that Delta Np63 has a dual-regulatory effect on the activity of its own promoter in NPC-076 cell. Down-regulation of the transcriptional activity is observed when Delta Np63 is present in low levels. In contrast, up-regulation of Delta Np63 transcriptional activity is observed when Delta Np63 is expressed at higher levels. The down-regulation effect is abolished when the p53-binding site of the Delta Np63 promoter is mutated. In sharp contrast, similar mutation does not affect the up-regulation of the Delta Np63 transcriptional activity under the same experimental conditions. Further study shows that the upregulation is correlated with the activation of the STAT3, as the blockade of STAT3 nuclear translocation abolishes the up-regulation by Delta Np63. Thus, Delta Np63 exerts a bidirectional regulation of the Delta Np63 transcriptional activity in NPC-076 cell. (c) 2006 Elsevier Inc. All rights reserved.