通过降低端粒酶逆转录酶（TERT）的多聚（ADP-核糖基）化以及敲低多聚（ADP-核糖）聚合酶-1（PARP-1）基因的HeLa细胞中TEP1/TP1的表达来抑制端粒酶活性。
Inhibition of telomerase activity by reduction of poly(ADP-ribosyl)ation of TERT and TEP1/TP1 expression in HeLa cells with knocked down poly(ADP-ribose) polymerase-1 (PARP-1) gene.
作者信息
Ghosh Utpal, Das Nilanjana, Bhattacharyya Nitai P
机构信息
Department of Biochemistry & Biophysics, University of Kalyani, Kalyani, Nadia 741235, India.
出版信息
Mutat Res. 2007 Feb 3;615(1-2):66-74. doi: 10.1016/j.mrfmmm.2006.10.002. Epub 2006 Dec 1.
Inhibitors of poly(ADP-ribose) polymerase (PARP) have been shown to reduce the telomerase activity in cultured cells. To find out the specific member of the PARP family, which participates in the regulation of telomerase activity, in the present investigation, we knocked down the PARP-1 gene by siRNA in HeLa cells and studied the telomerase activity. Reduction of expression of PARP-1 by siRNA increased cellular NAD(+) level and decreased general poly(ADP-ribosyl)ation of proteins. Telomerase activity decreased in cells with knocked down PARP-1 gene. Besides, we observed that telomerase reverse transcriptase (hTERT) was poly(ADP-ribosyl)ated in HeLa cells and such modification was decreased in cells with reduced PARP-1 expression. In addition, the expression of telomerase-associated protein 1 (TEP1/TP1) subunit of human telomerase holoenzyme reduced significantly in PARP-1 knock down HeLa cells. Thus, PARP-1 modulates the telomerase activity by altering poly(ADP-ribosyl)ation of TERT and/or the expression of TEP1/TP1.
聚（ADP - 核糖）聚合酶（PARP）抑制剂已被证明可降低培养细胞中的端粒酶活性。为了找出参与端粒酶活性调节的PARP家族特定成员，在本研究中，我们通过小干扰RNA（siRNA）敲低HeLa细胞中的PARP - 1基因，并研究端粒酶活性。siRNA使PARP - 1表达降低，增加了细胞内烟酰胺腺嘌呤二核苷酸（NAD(+)）水平，并减少了蛋白质的总体聚（ADP - 核糖）基化。PARP - 1基因敲低的细胞中端粒酶活性降低。此外，我们观察到HeLa细胞中端粒酶逆转录酶（hTERT）发生了聚（ADP - 核糖）基化，而在PARP - 1表达降低的细胞中这种修饰减少。另外，人端粒酶全酶的端粒酶相关蛋白1（TEP1/TP1）亚基的表达在PARP - 1敲低的HeLa细胞中显著降低。因此，PARP - 1通过改变TERT的聚（ADP - 核糖）基化和/或TEP1/TP1的表达来调节端粒酶活性。
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