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PXD039830-1

PXD039830 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleQuantitative proteomics and RNA-sequencing of mouse liver endothelial cells identify novel regulators of BMP6 by iron
DescriptionIron induces hepcidin by activating bone morphogenetic protein (BMP)6-SMAD signaling. Liver endothelial cells (LECs) produce BMP6, but the molecular mechanisms are incompletely understood. To address this, we performed proteomics and RNA-sequencing on LECs from iron-adequate and iron-loaded mice. Gene set enrichment analysis identified transcription factors activated by high iron, including Nrf-2, which was previously reported to contribute to BMP6 regulation, and proto-oncogene c-Jun (encoded by Jun). Jun knockdown blocked Bmp6, but not Nrf-2 pathway, induction by iron in LEC cultures. Moreover, chromatin immunoprecipitation of mouse livers showed iron-dependent c-Jun binding to predicted sites in Bmp6 regulatory regions. Finally, c-Jun inhibitor blunted induction of Bmp6 and hepcidin, but not Nrf-2 activity, in iron-loaded mice. However, Bmp6 expression and iron parameters were unchanged in endothelial Jun knockout mice. Our data suggest that c-Jun participates in iron-mediated BMP6 regulation independent of Nrf-2, though the mechanisms may be redundant and/or multifactorial.
HostingRepositoryPRIDE
AnnounceDate2023-12-28
AnnouncementXMLSubmission_2023-12-28_11:04:42.112.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJoao Paulo
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos; Orbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-02-03 06:03:30ID requested
12023-12-28 11:04:42announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Iron homeostasis, endothelial cells, liver, c-Jun, bone morphogenetic proteins
Contact List
Jodie L Babitt
contact affiliationNephrology Division and Endocrine Unit Massachusetts General Hospital Harvard Medical School Boston, MA
contact emailBabitt.jodie@mgh.harvard.edu
lab head
Joao Paulo
contact affiliationHarvard Medical School
contact emailjoao_paulo@post.harvard.edu
dataset submitter
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Dataset FTP location
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