E2F1 Transcription is Induced by Genotoxic Stress Through ATM/ATR Activation
E2F1 Transcription is Induced by Genotoxic Stress Through ATM/ATR Activation
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DOI：
10.1002/iub.197
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发表时间：
2009-05-01
期刊：
影响因子：
4.6
通讯作者：
Canepa, Eduardo T.
中科院分区：
文献类型：
--
作者：
Carcagno, Abel L.;Ogara, Maria F.;Canepa, Eduardo T.
E2 F1是转录因子E2 F家族的成员，在控制细胞周期进程和响应DNA损伤和癌基因激活的凋亡性细胞死亡中起关键作用。在遗传毒性胁迫后，E2 F1蛋白通过磷酸化和乙酰化稳定，从而驱动其积累。本工作的目的是检查是否增加E2 F1蛋白水平的DNA损伤后观察到的只是E2 F1蛋白的稳定性增加的反映，还是E2 F1基因的转录增强的结果。本文所提供的数据表明，紫外线和其他遗传毒性物质以ATM/ATR依赖的方式诱导E2 F1基因的转录，从而导致E2 F1 mRNA和蛋白水平的增加。在基因毒性胁迫后，E2 F1靶基因cyclin E的转录被显著诱导。这种诱导是两种分化良好的作用的结果，其中一种依赖于从头蛋白质合成，另一种依赖于蛋白质稳定。我们的研究结果强烈支持DNA损伤剂对E2 F1表达的转录作用。本文提出的结果揭示了一个新的机制，涉及E2 F1在响应遗传毒性应激。(C)2009 IUBMB IUBMB Life，61（5）：537-543，2009
E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well-differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress. (C) 2009 IUBMB IUBMB Life, 61(5): 537-543, 2009