PXD055640-1

PXD055640 is an original dataset announced via ProteomeXchange.

Title	Hyperactive 20S Proteasome Enhances Proteostasis and ERAD in C. elegans via degradation of Intrinsically Disordered Proteins
Description	Age-related proteinopathies, including Alzheimer’s and Parkinson’s disease, are driven by toxic accumulation of misfolded and intrinsically disordered proteins (IDPs) that overwhelm cellular proteostasis. The proteasome clears these proteins, but its failure in disease remains unclear. We engineered a Caenorhabditis elegans model with a hyperactive 20S proteasome (α3ΔN) for selective 20S activation. α3ΔN markedly enhanced IDP and misfolded protein degradation, reduced oxidative damage, and improved endoplasmic reticulum associated degradation (ERAD). Aggregation prone substrates such as vitellogenins and human alpha-1 antitrypsin (ATZ) were efficiently cleared. Integrated proteomic and transcriptomic analyses reveal systemic adaptations featuring increased protein turnover and oxidative stress resistance independent of superoxide dismutases (SODs). Strikingly, α3ΔN extended lifespan and stress resistance independently of canonical unfolded protein response (UPR) signaling via xbp 1. These findings substantiate a “20S pathway” of proteostasis that directly alleviates protein aggregation and oxidative stress, offering a promising therapeutic angle for neurodegenerative diseases
HostingRepository	PRIDE
AnnounceDate	2025-07-23
AnnouncementXML	Submission_2025-07-23_08:14:52.230.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Salcedo Tacuma
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-06 11:39:56	ID requested
⏵ 1	2025-07-23 08:14:53	announced

10.1101/2024.04.04.588128;

Salcedo-Tacuma D, Asad N, Anderson R, Smith DM, via degradation of Intrinsically Disordered Proteins. bioRxiv, ():(2025) [pubmed]

submitter keyword: Proteasome degradation c.elegans TMT-MS proteostasis ERAD

David M.Smith
contact affiliation	School of Medicine, Departement of Biochemistry and Molecular Medicine, West Virginia University, Morgantown U.S.
contact email	dmsmith@hsc.wvu.edu
lab head
David Salcedo Tacuma
contact affiliation	Graduate Student
contact email	drs00014@mix.wvu.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/07/PXD055640

PRIDE project URI

• PRIDE
  1. PXD055640
     1. Label: PRIDE project
     2. Name: Hyperactive 20S Proteasome Enhances Proteostasis and ERAD in C. elegans via degradation of Intrinsically Disordered Proteins