PXD055227

PXD055227 is an original dataset announced via ProteomeXchange.

Title	Temporal control of acute protein aggregate turnover by UBE3C and NRF1-dependent proteasomal pathways
Description	A hallmark of neurodegenerative diseases such as Parkinson’s Disease is the progressive loss of proteostasis, leading to the conversion of misfolded proteins into aggregates and subsequent cytotoxicity. To combat this toxicity, cells have evolved degradation pathways (ubiquitin-proteasome system and autophagy) that detect and degrade misfolded proteins. Here, we find that aggregation burden dictates the activation of proteasome-dependent quality control pathways. Initial misfolded proteins, enriched in oligomers, utilize UBE3C-dependent proteasomal degradation, while higher aggregation levels, enriched in larger insoluble structures, activate the NRF1 transcription factor to increase proteasome subunit transcription, and subsequent degradation capacity of cells. The role of UBE3C and NRF1 in aggregation clearance may provide therapeutic targets aimed to preventing neurodegenerative disease.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_07:01:02.514.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kelsey Hickey
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-27 02:57:44	ID requested
1	2024-10-11 05:08:09	announced
⏵ 2	2024-10-22 07:01:02	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Ubiquitin-proteasome system, NRF1, Protein quality control, Protein aggregates,Protein turnover, UBE3C

Wade Harper
contact affiliation	Harvard Medical School
contact email	wade_harper@hms.harvard.edu
lab head
Kelsey Hickey
contact affiliation	HMS
contact email	kelsey_hickey@hms.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055227
     1. Label: PRIDE project
     2. Name: Temporal control of acute protein aggregate turnover by UBE3C and NRF1-dependent proteasomal pathways