Show simple item record

dc.contributor.authorChung, Jacky
dc.contributor.authorWittig, Johannes G
dc.contributor.authorGhamari, Alireza
dc.contributor.authorMaeda, Manami
dc.contributor.authorDailey, Tamara A
dc.contributor.authorBergonia, Hector
dc.contributor.authorKafina, Martin D
dc.contributor.authorCoughlin, Emma E
dc.contributor.authorMinogue, Catherine E
dc.contributor.authorHebert, Alexander S
dc.contributor.authorLi, Liangtao
dc.contributor.authorKaplan, Jerry
dc.contributor.authorLodish, Harvey F
dc.contributor.authorBauer, Daniel E
dc.contributor.authorOrkin, Stuart H
dc.contributor.authorCantor, Alan B
dc.contributor.authorMaeda, Takahiro
dc.contributor.authorPhillips, John D
dc.contributor.authorCoon, Joshua J
dc.contributor.authorPagliarini, David J
dc.contributor.authorDailey, Harry A
dc.contributor.authorPaw, Barry H
dc.date.accessioned2018-02-09T16:53:30Z
dc.date.available2018-02-09T16:53:30Z
dc.date.issued2017-05
dc.date.submitted2016-12
dc.identifier.issn2050-084X
dc.identifier.urihttp://hdl.handle.net/1721.1/113559
dc.description.abstractHeme is required for survival of all cells, and in most eukaryotes, is produced through a series of eight enzymatic reactions. Although heme production is critical for many cellular processes, how it is coupled to cellular differentiation is unknown. Here, using zebrafish, murine, and human models, we show that erythropoietin (EPO) signaling, together with the GATA1 transcriptional target, AKAP10, regulates heme biosynthesis during erythropoiesis at the outer mitochondrial membrane. This integrated pathway culminates with the direct phosphorylation of the crucial heme biosynthetic enzyme, ferrochelatase (FECH) by protein kinase A (PKA). Biochemical, pharmacological, and genetic inhibition of this signaling pathway result in a block in hemoglobin production and concomitant intracellular accumulation of protoporphyrin intermediates. Broadly, our results implicate aberrant PKA signaling in the pathogenesis of hematologic diseases. We propose a unifying model in which the erythroid transcriptional program works in concert with post-translational mechanisms to regulate heme metabolism during normal development.en_US
dc.description.sponsorshipNational Heart, Lung, and Blood Institute (Grant P01 HL032262)en_US
dc.publishereLife Sciences Publications, Ltden_US
dc.relation.isversionofhttp://dx.doi.org/10.7554/ELIFE.24767en_US
dc.rightsCreative Commons Attribution 4.0 International Licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourceeLifeen_US
dc.titleErythropoietin signaling regulates heme biosynthesisen_US
dc.typeArticleen_US
dc.identifier.citationChung, Jacky et al. “Erythropoietin Signaling Regulates Heme Biosynthesis.” eLife 2017, 6 (May 2017): e24767 © 2017 eLife Sciences Publications Ltden_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorLodish, Harvey F
dc.relation.journaleLifeen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-02-02T18:59:28Z
dspace.orderedauthorsChung, Jacky; Wittig, Johannes G; Ghamari, Alireza; Maeda, Manami; Dailey, Tamara A; Bergonia, Hector; Kafina, Martin D; Coughlin, Emma E; Minogue, Catherine E; Hebert, Alexander S; Li, Liangtao; Kaplan, Jerry; Lodish, Harvey F; Bauer, Daniel E; Orkin, Stuart H; Cantor, Alan B; Maeda, Takahiro; Phillips, John D; Coon, Joshua J; Pagliarini, David J; Dailey, Harry A; Paw, Barry Hen_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7029-7415
mit.licensePUBLISHER_POLICYen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record