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@ARTICLE{Figlia:303037,
      author       = {G. Figlia$^*$ and S. Müller$^*$ and F. Garcia-Cortizo$^*$
                      and M. Neff$^*$ and G. Klinke and G. Poschet and A.
                      Teleman$^*$},
      title        = {m{TORC}1 senses glutamine and other amino acids through
                      {GCN}2.},
      journal      = {The EMBO journal},
      volume       = {44},
      number       = {17},
      issn         = {0261-4189},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DKFZ-2025-01484},
      pages        = {4825-4866},
      year         = {2025},
      note         = {#EA:B140#LA:B140# / 2025 Sep;44(17):4825-4866},
      abstract     = {mTORC1 promotes cell growth when nutrients such as amino
                      acids are available. While dedicated sensors relaying
                      availability of leucine, arginine and methionine to mTORC1
                      have been identified, it is still unclear how mTORC1 senses
                      glutamine, one of its most potent inducers. Here, we find
                      that glutamine is entirely sensed through the protein kinase
                      GCN2, whose initial activation is not triggered by depletion
                      of glutamine itself, but by the concomitant depletion of
                      asparagine. In turn, GCN2 leads to a succession of events
                      that additively inhibit mTORC1: within 1 h, GCN2 inhibits
                      mTORC1 through the Rag GTPases, independently of its
                      function as an eIF2α kinase. Later, GCN2-mediated induction
                      of ATF4 upregulates Ddit4 followed by Sestrin2, which
                      together cause additional mTORC1 inhibition. Additionally,
                      we find that depletion of virtually any other amino acid
                      also inhibits mTORC1 through GCN2. GCN2 and the dedicated
                      amino acid sensors thus represent two independent systems
                      that enable mTORC1 to perceive a wide spectrum of amino
                      acids.},
      keywords     = {Amino Acid Sensors (Other) / Asparagine (Other) / GCN2
                      (Other) / Glutamine (Other) / mTORC1 (Other)},
      cin          = {B140},
      ddc          = {570},
      cid          = {I:(DE-He78)B140-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40691417},
      doi          = {10.1038/s44318-025-00505-1},
      url          = {https://inrepo02.dkfz.de/record/303037},
}