Transcriptional control of cystine/glutamate transporter gene by amino acid deprivation
Transcriptional control of cystine/glutamate transporter gene by amino acid deprivation
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DOI：
10.1016/j.bbrc.2004.10.009
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发表时间：
2004-12-03
影响因子：
3.1
通讯作者：
Bannai, S
中科院分区：
文献类型：
--
作者：
Sato, H;Nomura, S;Bannai, S
最近的研究表明，氨基酸的耗尽导致几个基因的诱导，并且称为氨基酸反应元件（AARE）的基因组顺式元件是诱导所必需的。系统XC是对胱氨酸和谷氨酸高度特异性的阴离子氨基酸转运系统，并且已知其活性由胱氨酸剥夺诱导。该转运蛋白由两种蛋白质组分xCT和4F 2重链组成，xCT被认为介导转运活性。在本研究中，通过氨基酸剥夺诱导xCT的分子机制进行了研究。在小鼠NIH 3 T3细胞中，系统xc和xCT mRNA的活性不仅通过剥夺胱氨酸诱导，而且通过剥夺其他氨基酸诱导。在小鼠xCT基因的5 '侧翼区发现了两个AARE，每个AARE位于相反的方向，具有插入序列。启动子分析表明，这两个AARES是必要的xCT mRNA的最大诱导响应氨基酸剥夺。缺糖对x（c）（-）系统活性的诱导无影响。电泳迁移率变动分析表明，ATF 4，而不是ATF 2，是参与氨基酸控制的xCT表达。这些结果表明，xCT是一个新成员的蛋白质，其转录调控的氨基酸剥夺是由AARE介导的。(C)2004年爱思唯尔公司All rights reserved.
Recent studies have demonstrated that depletion of amino acids results in the induction of several genes and that a genomic cis-element termed amino acid response element (AARE) is required for the induction. System x C is an anionic amino acid transport system highly specific for cystine and glutamate, and its activity is known to be induced by cystine deprivation. This transporter is composed of two protein components, xCT and 4F2 heavy chain, and xCT is thought to mediate the transport activity. In the present study, the molecular mechanism for the induction of xCT by amino acid deprivation has been investigated. In mouse NIH3T3 cells, the activity of system x c and xCT mRNA is induced not only by deprivation of cystine but also by deprivation of other amino acids. Two AAREs, each located in the opposite direction with an intervening sequence, were found in the 5'-flanking region of the mouse xCT gene. Promoter analysis revealed that both AAREs were necessary for the maximal induction of xCT mRNA in response to the amino acid deprivation. Glucose deprivation had no effect on the induction of the activity of system x(c)(-). Electrophoretic mobility shift assay showed that ATF4, but not ATF2, is involved in the amino acid control of xCT expression. These results demonstrate that xCT is a new member of the proteins whose transcriptional control by the amino acid deprivation is mediated by AARE. (C) 2004 Elsevier Inc. All rights reserved.