PXD027232

PXD027232 is an original dataset announced via ProteomeXchange.

Title	SIRT7-induced PHF5A de-crotonylation regulates ageing progress through alternative splicing-mediated downregulation of CDK2
Description	Dysregulation of protein post-translational modification (PTM) can lead to a variety of pathological process, such as abnormal sperm development, malignant tumorigenesis, depression, and ageing process. SIRT7 is a NAD + dependent protein deacetylase. Besides known deacetylation, SIRT7 may also have the capacity to remove other acylation. However, the roles of SIRT7-induced other de-acylation in ageing is still largely unknown. Here, we found that the expression of SIRT7 was significantly increased in senescent fibroblasts and aged tissues. Knockdown or overexpression of SIRT7 can inhibit or promote fibroblast senescence. Knockdown of SIRT7 led to increased pan- lysine crotonylation (Kcr) levels in senescent fibroblasts. Using modern mass spectrometry (MS) technology, we identified 5149 Kcr sites across 1541 protein in senescent fibroblasts, providing the largest crotonylome dataset to date in senescent cells. Specifically, among the identified protein, we found SIRT7 de-crotonylated PHF5A, an alternative splicing factor, at K25. De-crotonylation of PHF5A K25 contributed to decreased CDK2 expression by Retained Intron (RI) induced abnormal alternative splicing, thereby accelerating fibroblasts senescence, supporting a key role of PHF5A K25 de-crotonylation in ageing. Collectively, our data revealed the molecular mechanism of SIRT7-induced k25 decrotonylation of PHF5A regulating aging, and provide new ideas and molecular targets for drug intervention in cellular ageing and the treatment of aging-related diseases, indicating that protein crotonylation has important implication in the regulation of ageing progress.
HostingRepository	PRIDE
AnnounceDate	2022-02-17
AnnouncementXML	Submission_2022-02-17_03:12:46.307.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	zhixiao wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iTRAQ4plex-116 reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-12 01:42:23	ID requested
⏵ 1	2022-02-17 03:12:47	announced

Yu AQ, Wang J, Jiang ST, Yuan LQ, Ma HY, Hu YM, Han XM, Tan LM, Wang ZX, SIRT7-Induced PHF5A Decrotonylation Regulates Aging Progress Through Alternative Splicing-Mediated Downregulation of CDK2. Front Cell Dev Biol, 9():710479(2021) [pubmed]

submitter keyword: Human,fibroblasts,Crotonylation

zhixiao wang
contact affiliation	Department of Cardiology, the Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai 519100, Guangdong, P.R. China
contact email	zhixiaowang@whu.edu.cn
lab head
zhixiao wang
contact affiliation	the Fifth Affiliated Hospital of Zunyi Medical University
contact email	zhixiaowang@whu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027232
     1. Label: PRIDE project
     2. Name: SIRT7-induced PHF5A de-crotonylation regulates ageing progress through alternative splicing-mediated downregulation of CDK2