SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway
Name
nihms925589.pdf
Size
646.09 KB
Format
Adobe PDF
Checksum (MD5)
33d53ca0ba8c0e95af2ee048f45ad2b6
Author(s)
Harper, J. Wade
Gygi, Steven P.
Gu, Xin
Orozco Segrera, Jose
Saxton, Robert Andrew
Condon, Kendall Janine
Liu, Grace Yun
Krawczyk, Patrycja A.
Scaria, Sonia M.
Sabatini, David
Date Issued
November 2017
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Gu, Xin et al. “SAMTOR Is anS-Adenosylmethionine Sensor for the mTORC1 Pathway.” Science 358, no. 6364 (November 9, 2017): 813–818.
Version
Author's final manuscript
Abstract
mTOR complex 1 (mTORC1) regulates cell growth and metabolism in response to multiple environmental cues. Nutrients signal via the Rag guanosine triphosphatases (GTPases) to promote the localization of mTORC1 to the lysosomal surface, its site of activation. We identified SAMTOR, a previously uncharacterized protein, which inhibits mTORC1 signaling by interacting with GATOR1, the GTPase activating protein (GAP) for RagA/B. We found that the methyl donor S-adenosylmethionine (SAM) disrupts the SAMTOR-GATOR1 complex by binding directly to SAMTOR with a dissociation constant of approximately 7 μM. In cells, methionine starvation reduces SAM levels below this dissociation constant and promotes the association of SAMTOR with GATOR1, thereby inhibiting mTORC1 signaling in a SAMTOR-dependent fashion. Methionine-induced activation of mTORC1 requires the SAM binding capacity of SAMTOR. Thus, SAMTOR is a SAM sensor that links methionine and one-carbon metabolism to mTORC1 signaling.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/SCIENCE.AAO3265
