PXD020440-1

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

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