Identification of a novel DNA binding site and a transcriptional target for activating transcription factor 5 in c6 glioma and mcf-7 breast cancer cells.
Identification of a novel DNA binding site and a transcriptional target for activating transcription factor 5 in c6 glioma and mcf-7 breast cancer cells.
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DOI：
10.1158/1541-7786.mcr-08-0365
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发表时间：
2009-06
期刊：
影响因子：
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通讯作者：
Liu DX
中科院分区：
文献类型：
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作者：
Li G;Li W;Angelastro JM;Greene LA;Liu DX
最近的报道表明，转录激活因子5（ATF 5）是癌细胞生存所必需的，但非癌细胞则不需要。然而，ATF 5调节基因和促进细胞存活的机制尚不清楚。使用循环扩增和选择目标（CASTing）的方法，我们确定了一个新的ATF 5的共识DNA结合序列。我们在C6胶质瘤和MCF-7乳腺癌细胞中发现，ATF 5占据了该序列，并且ATF 5激活了由该位点驱动的报告基因表达。相反，当ATF 5活性被阻断或当ATF 5表达被血清戒断下调时，报告基因活性降低。我们进一步表明，早期生长反应因子1（Egr-1），其启动子包含两个相邻的ATF 5的共识结合位点在一个保守的启动子位置在大鼠，小鼠和人类，靶向和调节C6和MCF-7细胞中的ATF 5。这些数据为ATF 5促进基因调控和癌症特异性细胞存活的机制提供了新的见解。
Recent reports indicate that the activating transcription factor 5 (ATF5) is required for the survival of cancer cells but not for non-cancer cells. However, the mechanisms by which ATF5 regulates genes and promotes cell survival are not clear. Using a cyclic amplification and selection of targets (CASTing) approach, we identified a novel ATF5 consensus DNA binding sequence. We show in C6 glioma and MCF-7 breast cancer cells that ATF5 occupies this sequence and that ATF5 activates reporter gene expression driven by this site. Conversely, reporter activity is diminished when ATF5 activity is blocked or when ATF5 expression is down-regulated by serum withdrawal. We further show that the early growth response factor 1 (Egr-1), whose promoter contains two adjacent ATF5 consensus binding sites at a conserved promoter position in rat, mouse and human, is targeted and regulated by ATF5 in C6 and MCF-7 cells. These data provide new insight on the mechanisms by which ATF5 promotes gene regulation and cancer-specific cell survival.