THAP5 is a DNA-binding transcriptional repressor that is regulated in melanoma cells during DNA damage-induced cell death.

THAP5 is a DNA-binding transcriptional repressor that is regulated in melanoma cells during DNA damage-induced cell death.
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THAP5是一种DNA结合的转录阻遏物,在DNA损伤诱导的细胞死亡过程中,在黑色素瘤细胞中受调节。

DOI:
10.1016/j.bbrc.2010.11.092
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发表时间:
2011-01-07
影响因子:
3.1
通讯作者:
Zervos AS
Zervos AS
中科院分区:
生物学4区
文献类型:
--
作者:
Balakrishnan MP;Cilenti L;Ambivero C;Goto Y;Takata M;Turkson J;Li XS;Zervos AS

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THAP5 最初被分离为线粒体促凋亡 Omi/HtrA2 蛋白酶的特定相互作用子和底物。它是一种人锌指蛋白,其特征是在小鼠和大鼠中表达模式受限且缺乏直向同源物。 THAP5 的生物学功能尚不清楚,但我们之前的研究表明它可以调节肾细胞的 G2/M 转变,并可能参与与冠状动脉疾病 (CAD) 相关的人类心肌细胞死亡。在本报告中,我们扩展了对人类黑色素瘤细胞中 THAP5 的特性和功能的研究。 THAP5 在原代人黑色素细胞以及所有测试的黑色素瘤细胞系中表达。 THAP5 蛋白水平通过紫外线照射或顺铂治疗显着诱导,这些条件已知会导致 DNA 损伤。 THAP5 的诱导与凋亡细胞死亡的显着增加相关。此外,我们还发现 THAP5 是一种核蛋白,可以识别并结合特定的 DNA 基序。 THAP5 还可以抑制异源系统中报告基因的转录。我们的工作表明 THAP5 是一种 DNA 结合蛋白和转录抑制蛋白。此外,THAP5 具有促凋亡功能,并且在促进细胞死亡的条件下在黑色素瘤细胞中被诱导。
THAP5 was originally isolated as a specific interactor and substrate of the mitochondrial pro-apoptotic Omi/HtrA2 protease. It is a human zinc finger protein characterized by a restricted pattern of expression and the lack of orthologs in mouse and rat. The biological function of THAP5 is unknown but our previous studies suggest it could regulate G2/M transition in kidney cells and could be involved in human cardiomyocyte cell death associated with coronary artery disease (CAD). In this report, we expanded our studies on the properties and function of THAP5 in human melanoma cells. THAP5 was expressed in primary human melanocytes as well as in all melanoma cell lines that were tested. THAP5 protein level was significantly induced by UV irradiation or cisplatin treatment, conditions known to cause DNA damage. The induction of THAP5 correlated with a significant increase in apoptotic cell death. In addition, we show that THAP5 is a nuclear protein that could recognize and bind a specific DNA motif. THAP5 could also repress the transcription of a reporter gene in a heterologous system. Our work suggests that THAP5 is a DNA binding protein and a transcriptional repressor. Furthermore, THAP5 has a pro-apoptotic function and it was induced in melanoma cells under conditions that promoted cell death.
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