GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2 Journal Article


Authors: Ye, J.; Palm, W.; Peng, M.; King, B.; Lindsten, T.; Li, M. O.; Koumenis, C.; Thompson, C. B.
Article Title: GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2
Abstract: Mammalian cells possess two amino acid-sensing kinases: general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1). Their combined effects orchestrate cellular adaptation to amino acid levels, but how their activities are coordinated remains poorly understood. Here, we demonstrate an important link between GCN2 and mTORC1 signaling. Upon deprivation of various amino acids, activated GCN2 up-regulates ATF4 to induce expression of the stress response protein Sestrin2, which is required to sustain repression of mTORC1 by blocking its lysosomal localization. Moreover, Sestrin2 induction is necessary for cell survival during glutamine deprivation, indicating that Sestrin2 is a critical effector of GCN2 signaling that regulates amino acid homeostasis through mTORC1 suppression. © 2015 Ye et al.
Keywords: mtorc1; sestrin; amino acid deprivation; gcn2
Journal Title: Genes and Development
Volume: 29
Issue: 22
ISSN: 0890-9369
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2015-11-15
Start Page: 2331
End Page: 2336
Language: English
DOI: 10.1101/gad.269324.115
PROVIDER: scopus
PUBMED: 26543160
PMCID: PMC4691887
DOI/URL:
Notes: Export Date: 2 December 2015 -- Source: Scopus
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MSK Authors
  1. Min Peng
    5 Peng
  2. Ming Li
    67 Li
  3. Jiangbin Ye
    6 Ye
  4. Craig Bernie Thompson
    120 Thompson
  5. Wilhelm Philipp Palm
    9 Palm
  6. Bryan Christopher King
    4 King