PXD045122

PXD045122 is an original dataset announced via ProteomeXchange.

Title	Cdc48’s interactions play a role in the cellular oxidative response in an aging-dependent manner
Description	The cellular redox status has long been linked to different cellular functions, including protein quality control (PQC) and aging. The prominent molecular machine Cdc48 (p97/VCP in mammals) is one of the key players involved in PQC, shuttling misfolded proteins to degradation. Through a range of N-terminal interactions, Cdc48 recognizes ubiquitin-tagged proteins targeted for proteasomal degradation. Here, we show that yeast Cdc48 is a redox-switch protein, with oxidation of a thiol-switch in the conserved Cys115. Using redox mass spectrometry, we characterize the oxidation status of Cdc48’s cysteine residues in the shift from the early- to late-stationary stages. Cdc48’s interactome undergoes a proteomic-scale rearrangement following this oxidation and leads to an increased association with antioxidants. Moreover, we found that the oxidation status of Cys115 mediates the activity of Cdc48, its interaction with canonical cofactors such as Shp1, and subsequent involvement in maintaining protein homeostasis during chronological aging. This work not only points to a new thiol switch protein in the protein degradation pathway, but also defines new roles for Cdc48 in chronological aging.
HostingRepository	PRIDE
AnnounceDate	2025-05-28
AnnouncementXML	Submission_2025-05-28_12:51:46.614.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Meytal Radzinski
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	N-ethylmaleimide derivatized cysteine; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-05 17:51:19	ID requested
⏵ 1	2025-05-28 12:51:47	announced

Radzinski M, Oppenheim T, Yogev O, Levy A, Naomi MB, Kacen A, Merbl Y, Ravid T, Reichmann D, Cdc48 plays a crucial role in redox homeostasis through dynamic reshaping of its interactome during early stationary phase. Redox Biol, 84():103651(2025) [pubmed]

10.1016/j.redox.2025.103651;

submitter keyword: redox,yeast, aging

Dana Reichmann
contact affiliation	Dept. of Biological Chemistry,The Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem,Givat Ram Campus, Jerusalem, 91904, Israel
contact email	danare@mail.huji.ac.il
lab head
Meytal Radzinski
contact affiliation	Hebrew University of Jerusalem
contact email	meytal.radzinski@mail.huji.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045122
     1. Label: PRIDE project
     2. Name: Cdc48’s interactions play a role in the cellular oxidative response in an aging-dependent manner