PXD022752

PXD022752 is an original dataset announced via ProteomeXchange.

Title	Proteome glioma cell lines LC-MS/MS
Description	Mutations in isocitrate dehydrogenase 1 or 2 (IDH1/2) define glioma subtypes and are 38 considered primary events in gliomagenesis, impacting tumor epigenetics and metabolism. 39 IDH enzymes are crucial for the generation of reducing potential, yet the impact of the mutation 40 on the cellular antioxidant system is not understood. Here, we investigate how glutathione 41 (GSH) levels are maintained in IDH1 mutant gliomas, despite an altered NADPH/NADP 42 balance. We find that IDH1 mutant astrocytomas specifically upregulate cystathionine γ-lyase 43 (CSE), the enzyme responsible for cysteine production upstream of GSH biosynthesis. Genetic 44 and chemical interference with CSE in patient-derived glioma cells carrying the endogenous 45 IDH1 mutation, sensitized tumor cells to cysteine depletion, an effect not observed in IDH1 46 wild-type gliomas. This correlated with reduced GSH synthesis as shown by in vitro and in vivo 47 serine tracing and led to delayed tumor growth in mice. Thus we show that IDH1 mutant 48 astrocytic gliomas critically rely on NADPH-independent de novo GSH synthesis to maintain 49 the antioxidant defense, which uncovers a novel metabolic vulnerability in this dismal disease.
HostingRepository	PRIDE
AnnounceDate	2021-11-25
AnnouncementXML	Submission_2021-11-25_07:20:38.883.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Elena Martinez Garcia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-26 00:07:21	ID requested
⏵ 1	2021-11-25 07:20:39	announced

Dataset with its publication pending

submitter keyword: Human, glioma cells, IDH1wt, IDH1mutant, LC-MS/MS

Gunnar Dittmar
contact affiliation	Quantitative Biology Unit, Luxembourg Institute of Health,Luxembourg
contact email	gunnar.dittmar@lih.lu
lab head
Elena Martinez Garcia
contact affiliation	Quantitative Biology Unit. Luxembourg Institute of Health
contact email	elena.martinezgarcia@lih.lu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/11/PXD022752

PRIDE project URI

• PRIDE
  1. PXD022752
     1. Label: PRIDE project
     2. Name: Proteome glioma cell lines LC-MS/MS