Mechanism of metabolic control. Target of rapamycin signaling links nitrogen quality to the activity of the Rtg1 and Rtg3 transcription factors.
Mechanism of metabolic control. Target of rapamycin signaling links nitrogen quality to the activity of the Rtg1 and Rtg3 transcription factors.
复制标题
代谢控制机制。雷帕霉素信号传导的靶标将氮质量与RTG1和RTG3转录因子的活性联系起来。
DOI：
10.1083/jcb.151.4.863
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发表时间：
2000-11-13
影响因子：
7.8
通讯作者：
Powers, T
中科院分区：
文献类型：
--
作者：
Komeili, A;Wedaman, K P;O'Shea, E K;Powers, T
氨基酸的从头生物合成使用TCA循环提供的中间体，这些中间体必须通过倒排反应补充，以维持细胞的呼吸能力。对酿酒酵母的全基因组表达分析表明，在首选氮源谷氨酰胺或谷氨酸存在时，参与这些反应的许多基因被抑制。这些基因在含尿素或氨作为唯一氮源的培养基中的表达需要异二聚体bZip转录因子Rtg1和Rtg3，并与Rtg1p/Rtg3复合体从主要的细胞质位置重新分布到主要的核位置相关。该复合体的核输入需要细胞质蛋白Rtg2，这是之前鉴定的Rtg1和Rtg3的上游调节因子，而输出需要输入β家族成员Msn5。值得注意的是，Rtg1/Rtg3的核积累及其靶基因的表达是通过添加雷帕霉素（一种雷帕霉素靶蛋白（TOR）激酶的特异性抑制剂）诱导的。我们进一步证明Rtg3是一种磷酸化蛋白，其磷酸化状态在雷帕霉素治疗后发生变化。综上所述，这些结果表明，雷帕霉素信号传导的靶标通过将氮质量与不同转录因子的活性和亚细胞定位相结合来调节特定的回变反应。
De novo biosynthesis of amino acids uses intermediates provided by the TCA cycle that must be replenished by anaplerotic reactions to maintain the respiratory competency of the cell. Genome-wide expression analyses in Saccharomyces cerevisiae reveal that many of the genes involved in these reactions are repressed in the presence of the preferred nitrogen sources glutamine or glutamate. Expression of these genes in media containing urea or ammonia as a sole nitrogen source requires the heterodimeric bZip transcription factors Rtg1 and Rtg3 and correlates with a redistribution of the Rtg1p/Rtg3 complex from a predominantly cytoplasmic to a predominantly nuclear location. Nuclear import of the complex requires the cytoplasmic protein Rtg2, a previously identified upstream regulator of Rtg1 and Rtg3, whereas export requires the importin-β-family member Msn5. Remarkably, nuclear accumulation of Rtg1/Rtg3, as well as expression of their target genes, is induced by addition of rapamycin, a specific inhibitor of the target of rapamycin (TOR) kinases. We demonstrate further that Rtg3 is a phosphoprotein and that its phosphorylation state changes after rapamycin treatment. Taken together, these results demonstrate that target of rapamycin signaling regulates specific anaplerotic reactions by coupling nitrogen quality to the activity and subcellular localization of distinct transcription factors.