PXD060906-1

PXD060906 is an original dataset announced via ProteomeXchange.

Title	Aging-Associated Modulation of UFMylation Hampers Proteostasis in C. elegans
Description	The attachment of Post-Translational Modifications (PTMs) to proteins plays key roles in the regulation of the activity and stability of various proteins. Here we utilized the nematode Caenorhabditis elegans to test whether UFMylation, a PTM that was found to be essential for key biological functions, is involved in the regulation of aging and protein homeostasis (proteostasis). Our results indicate that reduced rate of UFMylation extends lifespan and mitigates the toxicity of aggregative proteins that underlie the development of neurodegenerative disorders in humans. Mass spectrometric analysis unveiled that UFMylation of aging-regulating proteins, including components of the nucleolar FIB-1-NOL-56 complex and the germline resident proteins CAR-1 and CGH-1, governs proteostasis across tissues. Functional analyses indicate that the proteostasis-regulating transcription factors DAF-16 and SKN-1 are crucial for the counter proteotoxic effect of reduced UFMylation which is mediated by reduced rate of aggregation and enhanced protein degradation. These insights highlight the important roles of PTMs in the regulation of proteostasis and point at research directions for the development of new therapies for neurodegenerative disorders.
HostingRepository	PRIDE
AnnounceDate	2026-03-23
AnnouncementXML	Submission_2026-03-23_11:47:13.723.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Reut Bruck-Haimson
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: NEWT:6239;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-17 23:10:19	ID requested
⏵ 1	2026-03-23 11:47:14	announced

10.21203/RS.3.RS-6064783/V1;

submitter keyword: UFMylation,Aging, lifespan, C. elegans, germline, proteostasis

Ehud Cohen
contact affiliation	The Henri and Erna Leir Professor for Research in Neurodegenerative Diseases, Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada (IMRIC), School of Medicine, The Hebrew University of Jerusalem, Israel.
contact email	ehudc@ekmd.huji.ac.il
lab head
Reut Bruck-Haimson
contact affiliation	The Hebrew University of Jerusalem
contact email	reut.bruck@mail.huji.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060906
     1. Label: PRIDE project
     2. Name: Aging-Associated Modulation of UFMylation Hampers Proteostasis in C. elegans