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PXD059758

PXD059758 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDiscovery of Chiral D2HG and L2HG mediated Protein O-2-Hydroxyglutarylation
DescriptionOncometabolites including D-2-hydroxyglutarate (D2HG) and L2HG have come under the spotlight due to their roles in promoting tumorigenesis. These oncometabolites dysregulate growth-signalling pathways by noncovalently interacting with key regulators. However, it is unclear whether D/L 2HG influence cellular functions through covalent protein modification. Here we discovered a novel type of posttranslational modification by a novel unbiased immobilized metal ion affinity chromatographic (IMAC) based strategy and further confirmed it as the O-2-Hydroxyglutarylation. We found D2HG modification undergo upregulation upon D2HG treatment or in IDH mutant cells, while L2HG modification upregulate upon L2HG treatment or in hypoxia environment. By differential proteomics, we distinguished the enantiomer D2HG and L2HG modifications and constructed D2HG and L2HG modification datasets, and some of them were validated by isotopic metabolic flux approach. Quantitative proteomics identified O-2-Hydroxyglutarylation sites in multiple functional proteins, including DNA replicators and responders to oxidative stress. Two kinase, MRCKA bearing D2HG modification at site S794 and SLK bearing L2HG at S719 have been identified and confirmed by synthetic peptide standards. Phosphoproteomics revealed that the phosphorylation level of MRCKA and SLK's substrate downregulated in D2HG and L2HG accumulated cells respectively, suggesting a inhibitory effect of 2HG modification on kinase. The discovery of O-2-Hydroxyglutarylation shed light on the intricate relationship between cancer progression and the oncometabolites D/L-2HG, opening new pathways for the development of more effective cancer treatments.
HostingRepositoryjPOST
AnnounceDate2025-01-25
AnnouncementXMLSubmission_2025-01-24_18:22:04.315.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterZheng Zhang
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListS-carboxamidomethyl-L-cysteine; L-methionine sulfoxide; unknown modification; unknown modification; O-phospho-L-serine; O-phospho-L-threonine; O4'-phospho-L-tyrosine
Instrumentinstrument
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-01-14 00:03:57ID requested
12025-01-24 18:22:04announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: D2HG, L2HG, PTM, O-2-Hydroxyglutarylation
Contact List
W. Andy Tao
lab head
Zheng Zhang
contact affiliationPurdue University
dataset submitter
Full Dataset Link List
jPOST dataset URI
Dataset FTP location
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