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PXD004108

PXD004108 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMouse liver regeneration quantitative proteomics
DescriptionThe liver is the only organ in mammals, which fully regenerates after injury. To identify novel regulators of liver regeneration, we performed quantitative large-scale proteomics analysis of subcellular fractions from normal versus regenerating mouse liver. Proteins of the ubiquitin-proteasome pathway were rapidly regulated by partial hepatectomy, with the ubiquitin ligase Nedd4-1 being among the top hits. Knock-down of Nedd4-1 in hepatocytes in vivo through nanoparticle-mediated delivery of siRNA caused severe liver damage after partial hepatectomy and impaired regeneration, resulting in liver failure. Mechanistically, we demonstrate that Nedd4-1 is required for efficient activation of Erk1/2 signaling by receptor tyrosine kinases involved in liver regeneration through inhibition of receptor internalization, thus controlling a major pro-mitogenic and cytoprotective signaling pathway in the regenerating liver. These results highlight the power of large-scale proteomics to identify key players in liver regeneration and the importance of posttranslational regulation of growth factor signaling in this process.
HostingRepositoryPRIDE
AnnounceDate2017-09-13
AnnouncementXMLSubmission_2017-09-13_00:36:56.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterUlrich auf dem Keller
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmethylthiolated residue; iTRAQ8plex-116 reporter+balance reagent acylated residue; monohydroxylated residue
InstrumentLTQ Orbitrap Velos; Q Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02016-05-06 00:52:07ID requested
12017-09-13 00:36:57announced
Publication List
Bachofner M, Speicher T, Bogorad RL, Muzumdar S, Derrer CP, H, ü, rlimann F, B, ö, hm F, Nanni P, Kockmann T, Kachaylo E, Meyer M, Padrissa-Alt, é, s S, Graf R, Anderson DG, Koteliansky V, Auf dem Keller U, Werner S, Large-Scale Quantitative Proteomics Identifies the Ubiquitin Ligase Nedd4-1 as an Essential Regulator of Liver Regeneration. Dev Cell, 42(6):616-625.e8(2017) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: mouse, liver regeneration, partial hepatectomy, iTRAQ, DIA
Contact List
Sabine Werner
contact affiliationETH Zurich
contact emailsabine.werner@biol.ethz.ch
lab head
Ulrich auf dem Keller
contact affiliationDepartment of Biology
contact emailulrich.aufdemkeller@biol.ethz.ch
dataset submitter
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Dataset FTP location
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