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论文类型：期刊论文

发表时间：2017-02-17

发表刊物：JOURNAL OF BIOLOGICAL CHEMISTRY

收录刊物：SCIE、EI、PubMed

卷号：292

期号：7

页面范围：2660-2669

ISSN号：0021-9258

关键字：Gcn2,Kog1,TOR complex (TORC),TORC1,amino acid,amino acid starvation,autophagy,histidine,uncharged tRNA,yeast

摘要：In eukaryotic cells, two conserved protein kinases, Gcn2 and TOR complex 1 (TORC1), couple amino acid conditions to protein translation. Gcn2 functions as an amino acid sensor and is activated by uncharged tRNAs that accumulate when intracellular amino acids are limited. Activated Gcn2 phosphorylates and inhibits eukaryotic initiation factor-2 alpha (eIF2 alpha), resulting in repression of general protein synthesis. Like Gcn2, TORC1 is also involved in sensing amino acid conditions. However, the underlying mechanism remains unclear. In the present study, we show that TORC1 is a direct target of Gcn2 kinase in the yeast Saccharomyces cerevisiae. In response to amino acid starvation, Gcn2 binds to TORC1 and phosphorylates Kog1, the unique regulatory subunit of TORC1, resulting in down-regulation of TORC1 kinase activity. In the absence of Gcn2, TORC1 signaling activity increases and becomes unresponsive to amino acid starvation. Our findings demonstrate that TORC1 is an effector of Gcn2 in amino acid signaling, hence defining a novel mechanism by which TORC1 senses amino acid starvation.