PXD020440

PXD020440 is an original dataset announced via ProteomeXchange.

Title	Insulin Signaling Regulates Longevity Through Protein Phosphorylation in Caenorhabditis elegans
Description	Insulin/IGF-1 Signaling (IIS) is known to constrain longevity by inhibiting the transcription factor FOXO. How phosphorylation mediated by IIS kinases regulates lifespan beyond FOXO remains unclear. Here, we profile IIS-dependent phosphorylation changes in a large-scale quantitative phosphoproteomic analysis of wild-type and three IIS mutant Caenorhabditis elegans strains. We quantify more than 15,000 phosphosites and find that 476 of these are differentially phosphorylated in the long-lived daf-2/insulin receptor mutant. We develop a machine learning-based method to prioritize 25 potential lifespan-related phosphosites. We perform validations to show that AKT-1 pT492 inhibits DAF-16/FOXO and compensates the loss of daf-2 function, that EIF-2α pS49 potently inhibits protein synthesis and daf-2 longevity, and that reduced phosphorylation of multiple germline proteins apparently transmits reduced DAF-2 signaling to the soma. In addition, an analysis of kinases with enriched substrates detects that casein kinase 2 (CK2) subunits negatively regulate lifespan. Our study reveals detailed functional insights into longevity.
HostingRepository	iProX
AnnounceDate	2021-06-10
AnnouncementXML	Submission_2023-03-02_19:08:02.586.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wenjun Li
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationList	phosphorylated residue
Instrument	Q Exactive; Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-20 00:08:05	ID requested
⏵ 1	2023-03-02 19:08:03	announced

Li WJ, Wang CW, Tao L, Yan YH, Zhang MJ, Liu ZX, Li YX, Zhao HQ, Li XM, He XD, Xue Y, Dong MQ, Insulin signaling regulates longevity through protein phosphorylation in Caenorhabditis elegans. Nat Commun, 12(1):4568(2021) [pubmed]

submitter keyword: phosphoproteomics, quantitative proteomics, metabolic labeling, SRM, insulin/IGF-1 signaling, functional phosphosites, Caenorhabditis elegans

Mengqiu Dong
contact affiliation	National Institute of Biological Sciences
contact email	dongmengqiu@nibs.ac.cn
lab head
Wenjun Li
contact affiliation	National Institute of Biological Sciences
contact email	liwenjun@nibs.ac.cn
dataset submitter

iProX dataset URI