title: General Control Nonderepressible 2 (GCN2) Kinase Inhibits Target of Rapamycin Complex 1 in Response to Amino Acid Starvation inSaccharomyces cerevisiae.
abstract: 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-2α (eIF2α), 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 yeastSaccharomyces cerevisiaeIn 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.
authors.affiliation: From the School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China.|the Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, and.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Yuan
authors.affiliation: the Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, and.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Guo
authors.affiliation: From the School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, China.|the Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, and.
authors.forename: Jiaoqi
authors.initials: J
authors.lastname: Gao
authors.affiliation: the Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, and.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhong
authors.affiliation: the Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, and.
authors.forename: Gonghong
authors.initials: G
authors.lastname: Yan
authors.affiliation: the Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, and.
authors.forename: Wangmeng
authors.initials: W
authors.lastname: Wu
authors.affiliation: the State Key Laboratories of Transducer Technology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yapeng
authors.initials: Y
authors.lastname: Chao
authors.affiliation: the Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, and yuj5@pitt.edu.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D015536:Down-Regulation; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D000596:Amino Acids; C515118:Kog1 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; C512912:GCN2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases
keywords: Gcn2; Kog1; TOR complex (TORC); TORC1; amino acid; amino acid starvation; autophagy; histidine; uncharged tRNA; yeast