PXD043248

PXD043248 is an original dataset announced via ProteomeXchange.

Title	Proximal proteomics connects NRF2 suppression to ZNF746/PARIS-driven oxidative stress and apoptosis in Parkinson’s disease
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2023-12-18
AnnouncementXML	Submission_2023-12-18_10:13:55.311.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kyle LaPak
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-23 10:15:55	ID requested
⏵ 1	2023-12-18 10:13:55	announced

10.1126/SCISIGNAL.ADI9018;

submitter keyword: ZNF746,NRF2, PRM, Parkinson's disease, PARIS, Oxidative stress

Michael Ben Major
contact affiliation	Cell Biology and Physiology, Washington University in St. Louis, United States
contact email	bmajor@wustl.edu
lab head
Kyle LaPak
contact affiliation	Washington University in St. Louis
contact email	kyle.lapak@wustl.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043248
     1. Label: PRIDE project
     2. Name: Proximal proteomics connects NRF2 suppression to ZNF746/PARIS-driven oxidative stress and apoptosis in Parkinson’s disease