Show simple item record

dc.contributor.authorCsibi, Alfred
dc.contributor.authorFendt, Sarah-Maria
dc.contributor.authorLi, Chenggang
dc.contributor.authorPoulogiannis, George
dc.contributor.authorChoo, Andrew Y.
dc.contributor.authorChapski, Douglas J.
dc.contributor.authorJeong, Seung Min
dc.contributor.authorDempsey, Jamie M.
dc.contributor.authorParkhitko, Andrey
dc.contributor.authorMorrison, Tasha
dc.contributor.authorHenske, Elizabeth P.
dc.contributor.authorHaigis, Marcia C.
dc.contributor.authorCantley, Lewis C.
dc.contributor.authorStephanopoulos, Gregory
dc.contributor.authorYu, Jane
dc.contributor.authorBlenis, John
dc.date.accessioned2014-11-07T19:16:59Z
dc.date.available2014-11-07T19:16:59Z
dc.date.issued2013-05
dc.date.submitted2013-03
dc.identifier.issn00928674
dc.identifier.issn1097-4172
dc.identifier.urihttp://hdl.handle.net/1721.1/91506
dc.description.abstractProliferating mammalian cells use glutamine as a source of nitrogen and as a key anaplerotic source to provide metabolites to the tricarboxylic acid cycle (TCA) for biosynthesis. Recently, mammalian target of rapamycin complex 1 (mTORC1) activation has been correlated with increased nutrient uptake and metabolism, but no molecular connection to glutaminolysis has been reported. Here, we show that mTORC1 promotes glutamine anaplerosis by activating glutamate dehydrogenase (GDH). This regulation requires transcriptional repression of SIRT4, the mitochondrial-localized sirtuin that inhibits GDH. Mechanistically, mTORC1 represses SIRT4 by promoting the proteasome-mediated destabilization of cAMP-responsive element binding 2 (CREB2). Thus, a relationship between mTORC1, SIRT4, and cancer is suggested by our findings. Indeed, SIRT4 expression is reduced in human cancer, and its overexpression reduces cell proliferation, transformation, and tumor development. Finally, our data indicate that targeting nutrient metabolism in energy-addicted cancers with high mTORC1 signaling may be an effective therapeutic approach.en_US
dc.description.sponsorshipGerman Science Foundation (Fellow FE-1185)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2013.04.023en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceElsevier Open Archiveen_US
dc.titleThe mTORC1 Pathway Stimulates Glutamine Metabolism and Cell Proliferation by Repressing SIRT4en_US
dc.typeArticleen_US
dc.identifier.citationCsibi, Alfred, Sarah-Maria Fendt, Chenggang Li, George Poulogiannis, Andrew Y. Choo, Douglas J. Chapski, Seung Min Jeong, et al. “The mTORC1 Pathway Stimulates Glutamine Metabolism and Cell Proliferation by Repressing SIRT4.” Cell 153, no. 4 (May 2013): 840–854. © 2013 Elsevier Inc.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.mitauthorFendt, Sarah-Mariaen_US
dc.contributor.mitauthorStephanopoulos, Gregoryen_US
dc.relation.journalCellen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsCsibi, Alfred; Fendt, Sarah-Maria; Li, Chenggang; Poulogiannis, George; Choo, Andrew Y.; Chapski, Douglas J.; Jeong, Seung Min; Dempsey, Jamie M.; Parkhitko, Andrey; Morrison, Tasha; Henske, Elizabeth P.; Haigis, Marcia C.; Cantley, Lewis C.; Stephanopoulos, Gregory; Yu, Jane; Blenis, Johnen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-6909-4568
mit.licensePUBLISHER_POLICYen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record