State Transitions in the TORC1 Signaling Pathway and Information Processing in Saccharomyces cerevisiae
State Transitions in the TORC1 Signaling Pathway and Information Processing in Saccharomyces cerevisiae
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DOI：
10.1534/genetics.114.168369
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发表时间：
2014-10-01
期刊：
影响因子：
3.3
通讯作者：
Capaldi, Andrew P.
中科院分区：
文献类型：
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作者：
Hallett, James E. Hughes;Luo, Xiangxia;Capaldi, Andrew P.
TOR 激酶复合物 I (TORC1) 是所有真核生物细胞生长和代谢的关键调节因子。先前的酵母研究表明，在氮和氨基酸饥饿条件下，三种 GTPasesGtr1、Gtr2 和 Rho1 与 TORC1 结合，阻断 S6 激酶 Sch9 的磷酸化并激活蛋白磷酸酶 2A (PP2A)。这导致 450 个 Sch9 依赖性蛋白质和核糖体合成基因下调，以及 100 个 PP2A 依赖性氮同化和氨基酸合成基因上调。在这里，使用带移测定和微阵列测量，我们表明 TORC1 通路还存在其他三种应激/饥饿状态。首先，在葡萄糖饥饿条件下，AMP 激活蛋白激酶 (AMPK/Snf1) 和至少一个其他因子将 TORC1 通路推入关闭状态，其中 Sch9 分支信号传导和 PP2A 分支信号传导均受到抑制。值得注意的是，即使细胞同时缺乏氮和葡萄糖，TORC1 通路仍处于葡萄糖饥饿（PP2A 抑制）状态。其次，在渗透胁迫下，MAPK Hog1/p38 驱动 TORC1 通路进入不同的状态，其中 Sch9 信号和 PP2A 分支信号被抑制，但 PP2A 分支信号仍然可以被氮饥饿激活。第三，在氧化应激和热应激中，TORC1-Sch9信号传导被阻断，同时PP2A分支信号传导减弱。总之，我们的数据表明，TORC1 通路充当信息处理中心，在不同条件下激活不同基因，以确保根据细胞的需求分配可用能量来驱动生长、氨基酸合成或应激反应。
TOR kinase complex I (TORC1) is a key regulator of cell growth and metabolism in all eukaryotes. Previous studies in yeast have shown that three GTPasesGtr1, Gtr2, and Rho1bind to TORC1 in nitrogen and amino acid starvation conditions to block phosphorylation of the S6 kinase Sch9 and activate protein phosphatase 2A (PP2A). This leads to downregulation of 450 Sch9-dependent protein and ribosome synthesis genes and upregulation of 100 PP2A-dependent nitrogen assimilation and amino acid synthesis genes. Here, using bandshift assays and microarray measurements, we show that the TORC1 pathway also populates three other stress/starvation states. First, in glucose starvation conditions, the AMP-activated protein kinase (AMPK/Snf1) and at least one other factor push the TORC1 pathway into an off state, in which Sch9-branch signaling and PP2A-branch signaling are both inhibited. Remarkably, the TORC1 pathway remains in the glucose starvation (PP2A inhibited) state even when cells are simultaneously starved for nitrogen and glucose. Second, in osmotic stress, the MAPK Hog1/p38 drives the TORC1 pathway into a different state, in which Sch9 signaling and PP2A-branch signaling are inhibited, but PP2A-branch signaling can still be activated by nitrogen starvation. Third, in oxidative stress and heat stress, TORC1-Sch9 signaling is blocked while weak PP2A-branch signaling occurs. Together, our data show that the TORC1 pathway acts as an information-processing hub, activating different genes in different conditions to ensure that available energy is allocated to drive growth, amino acid synthesis, or a stress response, depending on the needs of the cell.