Maruyama Ryuto, Shimizu Makoto, Ishijima Tomoko, Nakai Yuji, Inoue Jun, Sato Ryuichiro
a Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences , The University of Tokyo , Tokyo , Japan.
b Institute for Food Sciences , Hirosaki University , Aomori , Japan.
Biosci Biotechnol Biochem. 2016 Jun;80(6):1149-54. doi: 10.1080/09168451.2016.1146072. Epub 2016 Mar 11.
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 identified C12orf39, CSTA, and CALCB as 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 activated C12orf39 promoter activity and that this activation was diminished by deletion or mutation of the AARE sequence in the promoter region. Our results suggest that C12orf39, CSTA, and CALCB are novel ATF4 target genes and that C12orf39 promoter activity is activated by ATF4 through AARE.
活化转录因子4（ATF4）是一种具有重要生物活性的转录因子。ATF4可由各种应激诱导产生，如内质网应激，通过真核生物翻译起始因子2α的磷酸化来实现。ATF4也参与脂质代谢。在本研究中，我们进行了一项微阵列实验，以鉴定新的ATF4靶基因，特别是那些参与脂质代谢的基因，并确定C12orf39、CSTA和CALCB为新的ATF4靶基因。这些基因的启动子区域存在作为ATF4结合位点的氨基酸反应元件（AARE）。在使用荧光素酶测定的详细分析中，我们表明ATF4激活了C12orf39启动子活性，并且该激活通过启动子区域中AARE序列的缺失或突变而减弱。我们的结果表明，C12orf39、CSTA和CALCB是新的ATF4靶基因，并且C12orf39启动子活性通过AARE被ATF4激活。
