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人类TP53基因5'侧翼区域的特征及其对天然化合物白藜芦醇的反应。

Characterization of the 5'-flanking region of the human TP53 gene and its response to the natural compound, Resveratrol.

作者信息

Uchiumi Fumiaki, Shoji Koichiro, Sasaki Yuki, Sasaki Moe, Sasaki Yamato, Oyama Takahiro, Sugisawa Kyoko, Tanuma Sei-ichi

机构信息

Department of Gene Regulation, Faculty of Pharmaceutical Sciences; Research Center for RNA Science, RIST;

Department of Gene Regulation, Faculty of Pharmaceutical Sciences;

出版信息

J Biochem. 2016 Apr;159(4):437-47. doi: 10.1093/jb/mvv126. Epub 2015 Dec 17.

Abstract

Tumour suppressor p53, which is encoded by theTP53gene, is widely known to play an important role in response to DNA damage and various stresses. It has recently been reported that p53 regulates glucose metabolism and that an increase in p53 protein level is induced after serum deprivation or treatments with a natural compound,trans-Resveratrol (Rsv). In this study, we constructed a Luciferase expression vector, pGL4-TP53-551, containing 551 bp of the 5'-upstream region of the humanTP53gene, which was then transfected into HeLa S3 cells. A Luciferase assay showed that Rsv treatment increased the promoter activity of theTP53gene in comparison to that ofPIF1 Detailed deletion and mutation analyses revealed that Nkx-2.5 and E2F-binding elements are required in addition to duplicated GGAA (TTCC), for the regulation ofTP53promoter activity. In this study, it is suggested that the transient induction ofTP53gene expression by Rsv treatment might be partly involved in its anti-aging effect through maintenance of chromosomal DNAs.

摘要

肿瘤抑制因子p53由TP53基因编码,众所周知,它在应对DNA损伤和各种应激反应中发挥重要作用。最近有报道称,p53调节葡萄糖代谢,血清剥夺或用天然化合物反式白藜芦醇(Rsv)处理后,p53蛋白水平会升高。在本研究中,我们构建了一个荧光素酶表达载体pGL4 - TP53 - 551,其包含人TP53基因5'上游区域的551 bp,然后将其转染到HeLa S3细胞中。荧光素酶分析表明,与PIF1相比,Rsv处理增加了TP53基因的启动子活性。详细的缺失和突变分析表明,除了重复的GGAA(TTCC)外,Nkx - 2.5和E2F结合元件对于TP53启动子活性的调节也是必需的。在本研究中,提示Rsv处理对TP53基因表达的短暂诱导可能通过维持染色体DNA部分参与其抗衰老作用。

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