Nutrient regulates Tor1 nuclear localization and association with rDNA promoter
Nutrient regulates Tor1 nuclear localization and association with rDNA promoter
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DOI：
10.1038/nature05020
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发表时间：
2006-08-31
期刊：
影响因子：
64.8
通讯作者：
Zheng, X. F. Steven
中科院分区：
文献类型：
--
作者：
Li, Hong;Tsang, Chi Kwan;Zheng, X. F. Steven
Tor是免疫抑制剂雷帕霉素的靶点，也是细胞生长的关键调节因子。它调节细胞质和细胞核(1-5)中不同的细胞过程，包括氨基酸转运体、核糖体RNA和核糖体蛋白的表达。尽管最近取得了相当大的进展，但人们对TOR信号的时空调控知之甚少，特别是对进入核团的调控。在这里，我们发现Tor1在酵母中动态地分布在细胞质和细胞核中。Tor1的核定位是营养依赖的，对雷帕霉素敏感：饥饿或雷帕霉素处理会导致Tor1退出细胞核。Tor1核定位对35S rRNA的合成至关重要，但对氨基酸转运蛋白和核糖体蛋白基因的表达并不重要。我们进一步证明Tor1以雷帕霉素和饥饿敏感的方式与35S核糖体DNA(RDNA)启动子染色质相关；这种关联是35S rRNA合成和细胞生长所必需的。这些结果表明，TOR复合体1(TORC1)的空间调控可能参与了其靶基因的差异调控。Tor是一种经典的胞质激酶，它通过控制转录因子的定位来介导胞浆到胞核的信号转导。我们的数据表明，TOR可能比之前认为的更密切地参与基因调控。
TOR is the target of the immunosuppressant rapamycin and a key regulator of cell growth. It modulates diverse cellular processes in the cytoplasm and nucleus(1-5), including the expression of amino acid transporters, ribosomal RNAs and ribosomal proteins. Despite considerable recent progress, little is known about the spatial and temporal regulation of TOR signalling, particularly that leading into the nucleus. Here we show that Tor1 is dynamically distributed in the cytoplasm and nucleus in yeast. Tor1 nuclear localization is nutrient dependent and rapamycin sensitive: starvation or treatment with rapamycin causes Tor1 to exit from the nucleus. Tor1 nuclear localization is critical for 35S rRNA synthesis, but not for the expression of amino acid transporters and ribosomal protein genes. We show further that Tor1 is associated with 35S ribosomal DNA ( rDNA) promoter chromatin in a rapamycin- and starvation-sensitive manner; this association is necessary for 35S rRNA synthesis and cell growth. These results indicate that the spatial regulation of TOR complex 1 (TORC1) might be involved in differential control of its target genes. TOR is known as a classic cytoplasmic kinase that mediates the cytoplasm-to-nucleus signalling by controlling the localization of transcription factors. Our data indicate that TOR might be more intimately involved in gene regulation than previously thought.