PXD037244-1

PXD037244 is an original dataset announced via ProteomeXchange.

Title	PDI-catalyzed oxidative protein folding mediates senescence by induction of ER-derived oxidative stress
Description	Protein homeostasis is linked with aging and aging associated diseases. Oxidative protein folding occurs in the endoplasmic reticulum (ER) and produces H2O2 as a byproduct. The role of oxidative protein folding in human stem cells aging remains unknown. Here, we succeed to knockout protein disulfide isomerase (PDI), a key oxidoreductase for catalyzing oxidative protein folding, in human embryonic stem cells (hESCs) and human mesenchymal stem cells (hMSCs). Deletion of PDI does not affect the self-renewal of hESCs but significantly delays hMSCs senescence. Mechanistically, knockout of PDI slows down the rate of oxidative protein folding and decreases the leakage of ER-derived H2O2 into the nucleus, therefore alleviating oxidative stress and the secretory-associated senescence phenotype (SASP). Among the SASP-related genes, SERPINE1 is identified as a key driver for cell senescence. These findings establish a novel link between oxidative protein folding and aging. The previously unrecognized function of PDI in regulating cell senescence provides a potential target for aging and aging-related disease intervention.
HostingRepository	PRIDE
AnnounceDate	2023-06-12
AnnouncementXML	Submission_2023-06-12_13:16:50.537.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	jizhao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-10 07:32:54	ID requested
⏵ 1	2023-06-12 13:16:50	announced
2	2023-11-14 09:01:07	announced	2023-11-14: Updated project metadata.

submitter keyword: human mesenchymal stem cells (hMSCs)

hydrogen peroxide (H2O2)

oxidative 29 protein folding

protein disulfide isomerase (PDI)

senescence

QianzhaoJi
contact affiliation	CAS（Chinese Academy of Sciences）
contact email	jiqianzhaonotold@outlook.com
lab head
jizhao
contact affiliation	17812007228
contact email	jiqianzhaonotold@outlook.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037244
     1. Label: PRIDE project
     2. Name: PDI-catalyzed oxidative protein folding mediates senescence by induction of ER-derived oxidative stress