PXD023479

PXD023479 is an original dataset announced via ProteomeXchange.

Title	Nuclear SIRT3 counteracts human stem cell senescence
Description	Sirtuin 3 (SIRT3) is an NAD+-dependent deacetylase involved in various physiological and pathological processes. However, the role of SIRT3 in regulating human stem cell senescence remains largely unknown. Here, we observed the downregulated expression of SIRT3 in senescent human mesenchymal stem cells (hMSCs). SIRT3 deficiency accelerated cellular senescence in hMSCs, along with compromised nuclear integrity, loss of heterochromatin and increased DNA damage. These aging-associated nuclear defects were attenuated by the reintroduction of SIRT3. Mechanistic studies demonstrated the interaction of SIRT3 with nuclear envelope proteins and heterochromatin-associated proteins. Further findings revealed that SIRT3 deficiency led to the loss of lamina-associated domains (LADs) from the nuclear lamina, increased chromatin accessibility and aberrant transcription of repetitive sequences. Meanwhile, the overexpression of nuclear-localized SIRT3 rescued the senescence phenotypes. Taken together, our study reveals a novel role of nuclear SIRT3 in stabilizing heterochromatin and counteracting hMSC senescence, which may provide new clinical therapeutic targets to ameliorate aging-related diseases.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_15:55:51.931.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ji zhao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-08 05:01:37	ID requested
⏵ 1	2021-09-09 15:55:52	announced

Diao Z, Ji Q, Wu Z, Zhang W, Cai Y, Wang Z, Hu J, Liu Z, Wang Q, Bi S, Huang D, Ji Z, Liu GH, Wang S, Song M, Qu J, SIRT3 consolidates heterochromatin and counteracts senescence. Nucleic Acids Res, 49(8):4203-4219(2021) [pubmed]

submitter keyword: SIRT3;stem cell;aging;LAD

Qianzhao Ji
contact affiliation	institute of zoology ,CAS
contact email	jiqianzhaonotold@outlook.com
lab head
ji zhao
contact affiliation	17812007228
contact email	jiqianzhaonotold@outlook.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023479
     1. Label: PRIDE project
     2. Name: Nuclear SIRT3 counteracts human stem cell senescence