p53 regulates Ki-67 promoter activity through p53-and Sp1-dependent manner in HeLa cells

p53 regulates Ki-67 promoter activity through p53-and Sp1-dependent manner in HeLa cells
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p53 在 HeLa 细胞中通过 p53 和 Sp1 依赖性方式调节 Ki-67 启动子活性

DOI:
10.1007/s13277-011-0191-4
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发表时间:
2011-10-01
期刊:
影响因子:
--
通讯作者:
Zheng, Jun-Nian
Zheng, Jun-Nian
中科院分区:
其他
文献类型:
--
作者:
Wang, Mei-Juan;Pei, Dong-Sheng;Zheng, Jun-Nian

文献摘要

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与细胞增殖密切相关的人Ki-67蛋白的表达受多种细胞介质的调节。在本研究中,我们研究了p53对Ki-67启动子在HeLa细胞中的作用,采用荧光素酶报告基因分析。结果表明:(1)p53以剂量依赖方式抑制Ki-67启动子活性;(2)p53结合基序通过与p53的序列特异性相互作用介导了Ki-67启动子的部分转录抑制作用;(3)p53能够抑制Sp1刺激的Ki-67启动子活性,(4)Sp1结合位点参与p53介导的Ki-67启动子转录抑制。结论:p53通过p53和Sp1依赖的途径抑制Ki-67启动子活性,p53和Sp1之间的相互作用可能参与了Ki-67的转录调控机制。
The expression of the human Ki-67 protein, which is strictly associated with cell proliferation, is regulated by a variety of cellular mediators. In this study, we studied the effects of p53 on Ki-67 promoter in HeLa cells using luciferase reporter assay. The results showed that: (1) p53 inhibited Ki-67 promoter activity in a dose-dependent manner, (2) the p53-binding motifs mediated part of the transcriptional repression of Ki-67 promoter through a sequence-specific interaction with p53, (3) p53 was able to repress the Sp1-stimulated Ki-67 promoter activity, and (4) the Sp1-binding sites were responsible for the p53-mediated transcriptional repression of Ki-67 promoter. In conclusion, p53 inhibited Ki-67 promoter activity via p53- and Sp1-dependent pathways, and the interaction between p53 and Sp1 might be involved in the transcriptional regulatory mechanisms.