The Sestrins Interact with GATOR2 to Negatively Regulate the Amino-Acid-Sensing Pathway Upstream of mTORC1
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Sabatini_The sestrins.pdf
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Author(s)
Chantranupong, Lynne
Orozco, Jose M.
Scaria, Sonia M.
Bar-Peled, Liron
Spooner, Eric
Isasa, Marta
Gygi, Steven P.
Sabatini, David M.
Wolfson, Rachel Laura
Saxton, Robert Andrew
Date Issued
September 2014
Journal
Cell Reports
Publisher
Elsevier
Citation
Chantranupong, Lynne, Rachel L. Wolfson, Jose M. Orozco, Robert A. Saxton, Sonia M. Scaria, Liron Bar-Peled, Eric Spooner, Marta Isasa, Steven P. Gygi, and David M. Sabatini. “The Sestrins Interact with GATOR2 to Negatively Regulate the Amino-Acid-Sensing Pathway Upstream of mTORC1.” Cell Reports 9, no. 1 (October 2014): 1–8.
Version
Final published version
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) kinase is a major regulator of cell growth that responds to numerous environmental cues. A key input is amino acids, which act through the heterodimeric Rag GTPases (RagA or RagB bound to RagC or RagD) in order to promote the translocation of mTORC1 to the lysosomal surface, its site of activation. GATOR2 is a complex of unknown function that positively regulates mTORC1 signaling by acting upstream of or in parallel to GATOR1, which is a GTPase-activating protein (GAP) for RagA or RagB and an inhibitor of the amino-acid-sensing pathway. Here, we find that the Sestrins, a family of poorly understood growth regulators (Sestrin1–Sestrin3), interact with GATOR2 in an amino-acid-sensitive fashion. Sestrin2-mediated inhibition of mTORC1 signaling requires GATOR1 and the Rag GTPases, and the Sestrins regulate the localization of mTORC1 in response to amino acids. Thus, we identify the Sestrins as GATOR2-interacting proteins that regulate the amino-acid-sensing branch of the mTORC1 pathway.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2014.09.014
