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dc.contributor.authorSon, Sungmin
dc.contributor.authorPark, Sojung
dc.contributor.authorLee, Huikyong
dc.contributor.authorSiddiqi, Farah
dc.contributor.authorLee, Jong Eun
dc.contributor.authorMenzies, Fiona M
dc.contributor.authorRubinsztein, David
dc.date.accessioned2018-09-21T15:21:44Z
dc.date.available2018-09-21T15:21:44Z
dc.date.issued2019-01-08
dc.identifier.issn1550-4131
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280631
dc.description.abstractThe mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a master regulator of cell growth and metabolism. Leucine (Leu) activates mTORC1 and many have tried to identify the mechanisms whereby cells sense Leu in this context. Here we describe that the Leu metabolite acetyl-coenzyme A (AcCoA) positively regulates mTORC1 activity by EP300-mediated acetylation of the mTORC1 regulator, Raptor, at K1097. Leu metabolism and consequent mTORC1 activity are regulated by intermediary enzymes. As AcCoA is a Leu metabolite, this process directly correlates with Leu abundance, and does not require Leu sensing via intermediary proteins, as has been described previously. Importantly, we describe that this pathway regulates mTORC1 in a cell-type-specific manner. Finally, we observed decreased acetylated Raptor, and inhibited mTORC1 and EP300 activity in fasted mice tissues. These results provide a direct mechanism for mTORC1 regulation by Leu metabolism.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCell Line
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectHumans
dc.subjectMice
dc.subjectAcetyl Coenzyme A
dc.subjectLeucine
dc.subjectFemale
dc.subjectMale
dc.subjectE1A-Associated p300 Protein
dc.subjectMechanistic Target of Rapamycin Complex 1
dc.subjectRegulatory-Associated Protein of mTOR
dc.titleLeucine Signals to mTORC1 via Its Metabolite Acetyl-Coenzyme A.
dc.typeArticle
prism.endingPage201.e7
prism.issueIdentifier1
prism.publicationDate2019
prism.publicationNameCell Metab
prism.startingPage192
prism.volume29
dc.identifier.doi10.17863/CAM.27997
dcterms.dateAccepted2018-08-12
rioxxterms.versionofrecord10.1016/j.cmet.2018.08.013
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-01
dc.contributor.orcidSon, Sungmin [0000-0002-3536-1952]
dc.contributor.orcidSiddiqi, Farah [0000-0001-9185-0163]
dc.contributor.orcidRubinsztein, David [0000-0001-5002-5263]
dc.identifier.eissn1932-7420
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idWellcome Trust (095317/Z/11/Z)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International