Identification and characterization of early growth response 2, a zinc-finger transcription factor, as a p53-regulated proapoptotic gene.
Identification and characterization of early growth response 2, a zinc-finger transcription factor, as a p53-regulated proapoptotic gene.
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DOI：
10.3892/ijo_00000792
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发表时间：
2010-12
影响因子：
5.2
通讯作者：
Ikuko Yokota;Y. Sasaki;Lisa Kashima;M. Idogawa;T. Tokino
中科院分区：
文献类型：
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作者：
Ikuko Yokota;Y. Sasaki;Lisa Kashima;M. Idogawa;T. Tokino
肿瘤抑制因子P53是一种转录因子，可在细胞应激状态下诱导细胞生长停滞和/或细胞凋亡。近年来，许多基因被鉴定为P53调控的基因；然而，没有一个单一的靶基因被证明是凋亡效应所必需的。利用基因芯片分析，我们已经确定转录因子早期生长反应2(EGR2)是p53家族的靶标，特别是P53、P63和P73。DNA损伤诱导的P53活性以及P53家族基因的过表达上调了EGR2的表达。此外，我们在EGR2基因中发现了一个对P53、TAp63和TAp73有反应的元件。这种反应元件在人类和啮齿动物之间高度保守。我们还发现，EGR2的过表达与抗癌药物联合使用可诱导细胞凋亡。相反，EGR2的失活减弱了P53介导的细胞凋亡。这些结果表明，EGR2是P53家族的直接转录靶点，可以部分地介导P53依赖的细胞凋亡途径。
Tumor suppressor p53 is a transcription factor that induces growth arrest and/or apoptosis in response to cellular stress. In recent years, many genes have been identified as p53-regulated genes; however, no single target gene has been shown to be required for the apoptotic effect. Using microarray analysis, we have identified the transcription factor early growth response 2 (EGR2) as a target of the p53 family, specifically p53, p63 and p73. EGR2 expression was up-regulated by DNA damage-induced p53 activity, as well as by overexpression of p53 family genes. Furthermore, we identified a responsive element to p53, TAp63, and TAp73 within the EGR2 gene. This response element is highly conserved between human and rodents. We also found that overexpression of EGR2 induced apoptosis when combined with anticancer agents. Conversely, inactivation of EGR2 attenuated p53-mediated apoptosis. The results presented here suggest that EGR2 is a direct transcriptional target of p53 family that can in part mediate the p53-dependent apoptotic pathway.