MCPH1/BRIT1 represses transcription of the human telomerase reverse transcriptase gene.
MCPH1/BRIT1 represses transcription of the human telomerase reverse transcriptase gene.
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DOI：
10.1016/j.gene.2011.12.053
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发表时间：
2012-03
期刊：
影响因子：
3.5
通讯作者：
Lei Shi;Ming Li;B. Su
中科院分区：
文献类型：
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作者：
Lei Shi;Ming Li;B. Su
MCPH 1是人端粒酶逆转录酶（hTERT）功能的抑制因子，参与细胞永生化。但是关于MCPH 1是如何抑制端粒酶活性的知之甚少。在这项研究中，以确定MCPH 1调节hTERT基因表达的机制，我们研究了MCPH 1在体外调节hTERT启动子的作用。将hTERT启动子与MCPH 1共转染Hela细胞，可抑制hTERT启动子的活性。EMSA实验证明MCPH 1可以与hTERT启动子近端结合。MCPH 1的过表达可抑制U2 OS细胞端粒酶活性，siRNA可阻断MCPH 1的表达。我们建议，MCPH 1的功能作为一个转录抑制剂的hTERT在体外。由于端粒酶的激活，广泛观察到在人类肿瘤细胞系，是肿瘤发生的关键步骤，我们的研究结果提供了新的见解描绘肿瘤抑制功能的MCPH 1通过下调hTERT/端粒酶的表达。
MCPH1, a repressor of human telomerase reverse transcriptase (hTERT) function, is implicated in cellular immortalization. But little is known about how MCPH1 represses telomerase activity. In this study, to determine the mechanism by which MCPH1 regulates hTERT gene expression, we examined the role of MCPH1 in regulating the hTERT promoter in vitro. Co-transfection of the hTERT promoter with MCPH1 in Hela cells could inhibit the hTERT promoter activity. The EMSA assay demonstrated that MCPH1 could bind to the proximal hTERT promoter. Overexpression of MCPH1 could repress telomerase activity, and the repression was abolished by knocking down the MCPH1 expression using siRNA in U2OS cells. We propose that MCPH1 functions as a transcriptional repressor of hTERT in vitro. Since the activation of telomerase, widely observed in human tumor cell lines, is a critical step in tumorigenesis, our findings provide new insights into delineating the tumor-suppressing function of MCPH1 through its down-regulation of hTERT/telomerase expression.