dc.contributor.author | Harper, J. Wade | |
dc.contributor.author | Gygi, Steven P. | |
dc.contributor.author | Gu, Xin | |
dc.contributor.author | Orozco Segrera, Jose | |
dc.contributor.author | Saxton, Robert Andrew | |
dc.contributor.author | Condon, Kendall Janine | |
dc.contributor.author | Liu, Grace Yun | |
dc.contributor.author | Krawczyk, Patrycja A. | |
dc.contributor.author | Scaria, Sonia M. | |
dc.contributor.author | Sabatini, David | |
dc.date.accessioned | 2019-01-24T21:30:24Z | |
dc.date.available | 2019-01-24T21:30:24Z | |
dc.date.issued | 2017-11 | |
dc.identifier.issn | 0036-8075 | |
dc.identifier.issn | 1095-9203 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/120131 | |
dc.description.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. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant R01 CA103866) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant R37 AI47389) | en_US |
dc.description.sponsorship | United States. Department of Defense (Grant W81XWH-07-0448) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Fellowship T32 GM007753) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant T32 GM007753) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant F30 CA210373) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant F31 GM121093-01A1) | en_US |
dc.description.sponsorship | National Science Foundation (U.S.) (Grant 2016197106) | en_US |
dc.description.sponsorship | Massachusetts Institute of Technology. Paul Gray UROP Fund (Grant 3143900) | en_US |
dc.publisher | American Association for the Advancement of Science (AAAS) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1126/SCIENCE.AAO3265 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Gu, Xin et al. “SAMTOR Is anS-Adenosylmethionine Sensor for the mTORC1 Pathway.” Science 358, no. 6364 (November 9, 2017): 813–818. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.department | Whitehead Institute for Biomedical Research | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Gu, Xin | |
dc.contributor.mitauthor | Orozco Segrera, Jose | |
dc.contributor.mitauthor | Saxton, Robert Andrew | |
dc.contributor.mitauthor | Condon, Kendall Janine | |
dc.contributor.mitauthor | Liu, Grace Yun | |
dc.contributor.mitauthor | Krawczyk, Patrycja A. | |
dc.contributor.mitauthor | Scaria, Sonia M. | |
dc.contributor.mitauthor | Sabatini, David | |
dc.relation.journal | Science | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2018-12-19T15:28:26Z | |
dspace.orderedauthors | Gu, Xin; Orozco, Jose M.; Saxton, Robert A.; Condon, Kendall J.; Liu, Grace Y.; Krawczyk, Patrycja A.; Scaria, Sonia M.; Harper, J. Wade; Gygi, Steven P.; Sabatini, David M. | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-3393-6927 | |
dc.identifier.orcid | https://orcid.org/0000-0002-4364-5912 | |
dc.identifier.orcid | https://orcid.org/0000-0002-9376-3984 | |
dc.identifier.orcid | https://orcid.org/0000-0002-9515-8892 | |
dc.identifier.orcid | https://orcid.org/0000-0002-1446-7256 | |
mit.license | OPEN_ACCESS_POLICY | en_US |