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dc.contributor.authorChung, Jacky
dc.contributor.authorBauer, Daniel Evan
dc.contributor.authorGhamari, Alireza
dc.contributor.authorNizzi, C. P.
dc.contributor.authorDeck, K. M.
dc.contributor.authorKingsley, P. D.
dc.contributor.authorYien, Yvette Yee
dc.contributor.authorHuston, N. C.
dc.contributor.authorChen, C.
dc.contributor.authorSchultz, I. J.
dc.contributor.authorDalton, Arthur J.
dc.contributor.authorWittig, Johannes
dc.contributor.authorPalis, J.
dc.contributor.authorOrkin, Stuart Holland
dc.contributor.authorLodish, H. F.
dc.contributor.authorEisenstein, R. S.
dc.contributor.authorCantor, Alan B.
dc.contributor.authorPaw, Barry Htin
dc.date.accessioned2017-08-15T18:50:48Z
dc.date.issued2015
dc.identifierQuick submit: 2015-06-05T01:07:01-04:00
dc.identifier.citationChung, J., D. E. Bauer, A. Ghamari, C. P. Nizzi, K. M. Deck, P. D. Kingsley, Y. Y. Yien, et al. 2015. “The mTORC1/4E-BP Pathway Coordinates Hemoglobin Production with L-Leucine Availability.” Science Signaling 8 (372) (April 14, 2015): ra34–ra34. doi:10.1126/scisignal.aaa5903.en_US
dc.identifier.issn1945-0877en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:33758681
dc.description.abstractIn multicellular organisms, the mechanisms by which diverse cell types acquire distinct amino acids and how cellular function adapts to their availability are fundamental questions in biology. We found that increased neutral essential amino acid (NEAA) uptake was a critical component of erythropoiesis. As red blood cells matured, expression of the amino acid transporter gene Lat3 increased, which increased NEAA import. Inadequate NEAA uptake by pharmacologic inhibition or RNAi-mediated knockdown of LAT3 triggered a specific reduction in hemoglobin production in zebrafish embryos and murine erythroid cells through the mTORC1 (mammalian target of rapamycin complex 1)/4E-BP (eukaryotic translation initiation factor 4E–binding protein) pathway. CRISPR-mediated deletion of members of the 4E-BP family in murine erythroid cells rendered them resistant to mTORC1 and LAT3 inhibition and restored hemoglobin production. These results identify a developmental role for LAT3 in red blood cells and demonstrate that mTORC1 serves as a homeostatic sensor that couples hemoglobin production at the translational level to sufficient uptake of NEAAs, particularly L-leucine.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Association for the Advancement of Science (AAAS)en_US
dc.relation.isversionofdoi:10.1126/scisignal.aaa5903en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pubmed/25872869en_US
dash.licenseOAP
dc.titleThe mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availabilityen_US
dc.typeJournal Articleen_US
dc.date.updated2015-06-05T05:07:15Z
dc.description.versionAccepted Manuscripten_US
dc.rights.holderChung J, Bauer DE, Ghamari A, Nizzi CP, Deck KM, Kingsley PD, Yien YY, Huston NC, Chen C, Schultz IJ, Dalton AJ, Wittig JG, Palis J, Orkin SH, Lodish HF, Eisenstein RS, Cantor AB, Paw BH.
dc.relation.journalScience Signalingen_US
dash.depositing.authorPaw, Barry Htin
dc.date.available2017-08-15T18:50:48Z
dc.identifier.doi10.1126/scisignal.aaa5903*
dash.authorsorderedfalse
dash.contributor.affiliatedWittig, Johannes
dash.contributor.affiliatedGhamari, Alireza
dash.contributor.affiliatedChung, Jacky
dash.contributor.affiliatedYien, Yvette
dash.contributor.affiliatedCantor, Alan
dash.contributor.affiliatedBauer, Daniel
dash.contributor.affiliatedPaw, Barry Htin
dash.contributor.affiliatedOrkin, Stuart


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