ReviewCell Biology

Sestrin regulation of TORC1: Is Sestrin a leucine sensor?

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Science Signaling  07 Jun 2016:
Vol. 9, Issue 431, pp. re5
DOI: 10.1126/scisignal.aaf2885


  • Fig. 1 The impact of Sestrins on amino acid–dependent TORC1 signaling.

    (A) Sestrins are transcriptionally induced in response to diverse types of environmental stress. (B) Once induced, Sestrins inhibit TORC1 signaling through activation of AMPK and modulation of the GATOR complexes. Two papers (37, 38) suggest that amino acid leucine disrupts the Sestrin2-GATOR2 interaction, thereby modulating the ability of Sestrin2 to inhibit TORC1 signaling. Additional molecules, such as leucyl-tRNA synthetase, GCN2, and SLC38A9, also play a role in mediating amino acid–dependent TORC1 regulation. eIF2α, eukaryotic translation initiation factor 2α.

  • Fig. 2 Structure comparison of human Sestrin2 in the absence [green; Protein Data Bank (PDB) ID: 5CUF] or presence (blue; PDB ID: 5DJ4) of leucine.

    The leucine-binding pocket is marked by the dashed oval. The calculated root mean square difference between the two structures is 0.70 Å based on the FATCAT server ( The illustration of protein structures was generated with PyMOL (DeLano Scientific LLC).

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