Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
Int J Oncol. 2010 Dec;37(6):1407-16. doi: 10.3892/ijo_00000792.
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.
肿瘤抑制因子 p53 是一种转录因子，可响应细胞应激诱导生长停滞和/或细胞凋亡。近年来，许多基因已被鉴定为 p53 调节基因；然而，尚无单一靶基因被证明对凋亡效应是必需的。通过微阵列分析，我们已经确定转录因子早期生长反应 2（EGR2）是 p53 家族（特别是 p53、p63 和 p73）的靶标。DNA 损伤诱导的 p53 活性以及 p53 家族基因的过表达均可上调 EGR2 的表达。此外，我们在 EGR2 基因内鉴定了一个响应 p53、TAp63 和 TAp73 的元件。该响应元件在人类和啮齿动物之间高度保守。我们还发现，当与抗癌药物联合使用时，过表达 EGR2 可诱导细胞凋亡。相反，EGR2 的失活可减弱 p53 介导的细胞凋亡。这里呈现的结果表明，EGR2 是 p53 家族的直接转录靶标，可部分介导 p53 依赖性凋亡途径。
