Searching for novel ATF4 target genes in human hepatoma cells by microarray analysis.
Searching for novel ATF4 target genes in human hepatoma cells by microarray analysis.
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通过微阵列分析在人肝癌细胞中寻找新的 ATF4 靶基因。
DOI：
10.1080/09168451.2016.1146072
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
and Sato R.
中科院分区：
文献类型：
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作者：
Maruyama R.;Shimizu M.;Ishijima T.;Nakai Y.;Inoue J.;and Sato R.
转录激活因子4（Activating Transcription Factor 4，ATF 4）是一种具有重要生物学活性的转录因子。ATF4是由内质网应激等多种应激反应通过真核生物翻译起始因子2α的磷酸化而诱导表达的。ATF4也参与脂质代谢。在本研究中，我们进行了微阵列实验，以确定新的ATF 4靶基因，特别是那些参与脂质代谢，并确定C12 orf39，CSTA，和CALCB作为新的ATF 4靶基因。作为ATF4结合位点的氨基酸应答元件（AARE）存在于这些基因的启动子区域中。在荧光素酶分析中，我们发现ATF4激活了C12orf39启动子活性，而启动子区AARE序列的缺失或突变会减弱这种激活。我们的研究结果表明C12orf39、CSTA和CALCB是新的ATF 4靶基因，并且C12orf39启动子活性通过AARE被ATF 4激活。
Activating transcription factor 4 (ATF4) is a transcription factor with an important biological activity. ATF4 is induced by various stresses, such as endoplasmic reticulum stress, through the phosphorylation of eukaryotic translation initiation factor 2α. ATF4 is also involved in lipid metabolism. In the present study, we performed a microarray experiment to identify new ATF4 target genes, particularly those involved in lipid metabolism, and identifiedC12orf39, CSTA,andCALCBas novel ATF4 target genes. An amino acid response element (AARE) as an ATF4-binding site is present in the promoter regions of these genes. In a detailed analysis using luciferase assay, we showed that ATF4 activatedC12orf39promoter activity and that this activation was diminished by deletion or mutation of the AARE sequence in the promoter region. Our results suggest thatC12orf39, CSTA,andCALCBare novel ATF4 target genes and thatC12orf39promoter activity is activated by ATF4 through AARE.