GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2

  • Ye J
  • Palm W
  • Peng M
 et al. 
  • 97

    Readers

    Mendeley users who have this article in their library.
  • 50

    Citations

    Citations of this article.

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.

Author-supplied keywords

  • Amino acid deprivation
  • GCN2
  • MTORC1
  • Sestrin

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Jiangbin Ye

  • Wilhelm Palm

  • Min Peng

  • Bryan King

  • Tullia Lindsten

  • Ming O. Li

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free