Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/101757
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Type: Journal article
Title: GCN2 contributes to mTORC1 inhibition by leucine deprivation through an ATF4 independent mechanism
Author: Averous, J.
Lambert-Langlais, S.
Mesclon, F.
Carraro, V.
Parry, L.
Jousse, C.
Bruhat, A.
Maurin, A.
Pierre, P.
Proud, C.
Fafournoux, P.
Citation: Scientific Reports, 2016; 6(1):27698-1-27698-10
Publisher: Nature Publishing Group
Issue Date: 2016
ISSN: 2045-2322
2045-2322
Statement of
Responsibility: 
Julien Averous, Sarah Lambert-Langlais, Florent Mesclon, Valérie Carraro, Laurent Parry, Céline Jousse, Alain Bruhat, Anne-Catherine Maurin, Philippe Pierre, Christopher G. Proud and Pierre Fafournoux
Abstract: It is well known that the GCN2 and mTORC1 signaling pathways are regulated by amino acids and share common functions, in particular the control of translation. The regulation of GCN2 activity by amino acid availability relies on the capacity of GCN2 to sense the increased levels of uncharged tRNAs upon amino acid scarcity. In contrast, despite recent progress in the understanding of the regulation of mTORC1 by amino acids, key aspects of this process remain unsolved. In particular, while leucine is well known to be a potent regulator of mTORC1, the mechanisms by which this amino acid is sensed and control mTORC1 activity are not well defined. Our data establish that GCN2 is involved in the inhibition of mTORC1 upon leucine or arginine deprivation. However, the activation of GCN2 alone is not sufficient to inhibit mTORC1 activity, indicating that leucine and arginine exert regulation via additional mechanisms. While the mechanism by which GCN2 contributes to the initial step of mTORC1 inhibition involves the phosphorylation of eIF2α, we show that it is independent of the downstream transcription factor ATF4. These data point to a novel role for GCN2 and phosphorylation of eIF2α in the control of mTORC1 by certain amino acids.
Keywords: Fibroblasts; Animals; Mice; Protein-Serine-Threonine Kinases; Arginine; Leucine; Eukaryotic Initiation Factor-2; Signal Transduction; Phosphorylation; Activating Transcription Factor 4; Embryo, Mammalian; Mechanistic Target of Rapamycin Complex 1
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
RMID: 0030049897
DOI: 10.1038/srep27698
Appears in Collections:Biochemistry publications

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