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PXD043182

PXD043182 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProximal proteomics connects NRF2 suppression to ZNF746/PARIS-driven oxidative stress and apoptosis in Parkinson’s disease
DescriptionThe nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor activates cytoprotective and metabolic gene expression in response to various electrophilic stressors. In disease, constitutive NRF2 activity promotes cancer progression while decreased NRF2 function contributes to neurodegenerative diseases. In contrast to the regulation of NRF2 protein stability in the cytoplasm, co-complexed proteins that govern NRF2 activity on chromatin are less clear. Using biotin proximity proteomics, we report networks for NRF2 and its family members NRF1, NRF3 and the NRF2 heterodimer MAFG. We found that the Parkinson’s disease zinc finger transcription factor ZNF746 (PARIS) physically associated with NRF2 and MAFG, resulting in suppression of NRF2-driven transcription. ZNF746 expression increased oxidative stress and apoptosis, phenotypes that were reversed by chemical and genetic hyperactivation of NRF2. This study presents a functionally annotated proximity network for NRF2 and suggests that ZNF746 overexpression in Parkinson’s disease directly inhibits NRF2-driven neuroprotection
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:17:57.241.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKyle LaPak
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListbiotinylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-06-21 15:54:20ID requested
12023-12-18 09:12:10announced
22024-10-22 06:17:57announced2024-10-22: Updated project metadata.
Publication List
10.1126/SCISIGNAL.ADI9018;
Keyword List
submitter keyword: ZNF746, Proximity proteomics, MAFG,NRF2, NRF3, NRF1, Parkinson's disease, Oxidative stress
Contact List
Michael Ben Major
contact affiliationDepartment of Cell Biology and Physiology, Washington University in St. Louis
contact emailbmajor@wustl.edu
lab head
Kyle LaPak
contact affiliationWashington University in St. Louis
contact emailkyle.lapak@wustl.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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