• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Translation of the yeast transcriptional activator GCN4 is stimulated by purine limitation: implications for activation of the protein kinase GCN2.
【24h】

Translation of the yeast transcriptional activator GCN4 is stimulated by purine limitation: implications for activation of the protein kinase GCN2.

机译：嘌呤限制刺激了酵母转录激活因子GCN4的翻译：对蛋白激酶GCN2激活的影响。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The transcriptional activator protein GCN4 is responsible for increased transcription of more than 30 different amino acid biosynthetic genes in response to starvation for a single amino acid. This induction depends on increased expression of GCN4 at the translational level. We show that starvation for purines also stimulates GCN4 translation by the same mechanism that operates in amino acid-starved cells, being dependent on short upstream open reading frames in the GCN4 mRNA leader, the phosphorylation site in the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha), the protein kinase GCN2, and translational activators of GCN4 encoded by GCN1 and GCN3. Biochemical experiments show that eIF-2 alpha is phosphorylated in response to purine starvation and that this reaction is completely dependent on GCN2. As expected, derepression of GCN4 in purine-starved cells leads to a substantial increase in HIS4 expression, one of the targets of GCN4 transcriptional activation. gcn mutants that are defective for derepression of amino acid biosynthetic enzymes also exhibit sensitivity to inhibitors of purine biosynthesis, suggesting that derepression of GCN4 is required for maximal expression of one or more purine biosynthetic genes under conditions of purine limitation. Analysis of mRNAs produced from the ADE4, ADE5,7, ADE8, and ADE1 genes indicates that GCN4 stimulates the expression of these genes under conditions of histidine starvation, and it appeared that ADE8 mRNA was also derepressed by GCN4 in purine-starved cells. Our results indicate that the general control response is more global than was previously imagined in terms of the type of nutrient starvation that elicits derepression of GCN4 as well as the range of target genes that depend on GCN4 for transcriptional activation.
机译：转录激活蛋白GCN4负责响应单个氨基酸的饥饿，增加30多种不同氨基酸的生物合成基因的转录。这种诱导取决于翻译水平上GCN4表达的增加。我们显示嘌呤的饥饿也通过在氨基酸饥饿的细胞中运行的相同机制刺激GCN4翻译，这取决于GCN4 mRNA前导子（真核翻译起始因子2的α亚基中的磷酸化位点）的短上游开放阅读框（eIF-2 alpha），蛋白激酶GCN2和由GCN1和GCN3编码的GCN4的翻译激活因子。生化实验表明，eIF-2α响应嘌呤饥饿而被磷酸化，该反应完全依赖于GCN2。不出所料，嘌呤饥饿细胞中GCN4的阻遏导致HIS4表达的实质性增加，而HIS4表达是GCN4转录激活的目标之一。有缺陷的氨基酸生物合成酶的阻抑作用的gcn突变体也表现出对嘌呤生物合成抑制剂的敏感性，这表明在嘌呤限制条件下，最大化表达一种或多种嘌呤生物合成基因需要GCN4的阻遏。对由ADE4，ADE5、7，ADE8和ADE1基因产生的mRNA的分析表明，在组氨酸饥饿的条件下，GCN4刺激了这些基因的表达，而且在嘌呤饥饿的细胞中，ADE8 mRNA也被GCN4抑制了。我们的结果表明，就引起GCN4抑制的营养饥饿类型以及依赖GCN4进行转录激活的靶基因范围而言，一般的控制反应比以前想象的更具全局性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号