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PXD025677

PXD025677 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEZH2-dependent transcriptional complex promotes aberrant epithelial remodelling after injury
DescriptionUnveiling the molecular mechanisms of tissue remodelling following injury is imperative to elucidate its regenerative capacity and aberrant repair in disease. Using different omics approaches, we identified enhancer of zester homolog 2 (EZH2) as a key regulator that initiates a fibrotic cascade in injured lung epithelium. Epithelial-injury-driven enrichment of nuclear transforming growth factor-b-activated kinase 1 (TAK1) mediates EZH2 phosphorylation to facilitate the release of EZH2 from polycomb repressive complex 2 (PRC2). This process leads to the establishment of a fibrotic transcriptional complex of EZH2, RNA-polymerase II (POL2) and nuclear actin, which orchestrates aberrant epithelial lung repair programs. The liberation of EZH2 from PRC2 is accompanied by an EZH2-EZH1 switch to preserve silencing at non-target genes. Loss of epithelial TAK1, EZH2 or blocking nuclear actin influx attenuates the fibrotic cascade and restores respiratory homeostasis. Accordingly, EZH2 inhibition significantly improves outcomes in a pulmonary fibrosis mouse model. Our results reveal an important non-canonical function of EZH2, paving the way for new therapeutic interventions in fibrotic lung diseases.
HostingRepositoryMassIVE
AnnounceDate2021-05-04
AnnouncementXMLSubmission_2021-05-04_07:47:32.862.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAlexandre Rosa Campos
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListOxidation; Acetyl
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-04-27 23:04:39ID requested
12021-05-04 07:47:33announced
Publication List
no publication
Keyword List
submitter keyword: Actin, EZH2, Lung fibrosis, RNA-polymerase II
Contact List
James Peter Garnett
contact affiliationBoehringer Ingelheim Pharma GmbH
contact emailjames.garnett@boehringer-ingelheim.com
lab head
Alexandre Rosa Campos
contact affiliationSBP Medical Discovery Institute
contact emailarosacampos@sbpdiscovery.org
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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