Proteomics

Dataset Information

0

Proteome glioma cell lines LC-MS/MS


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Elena Martinez Garcia  

LAB HEAD: Gunnar Dittmar

PROVIDER: PXD022752 | Pride | 2021-11-25

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
OxidationMSites.txt Txt
QHF_00005762_MQQC_HS_EMG_421L.raw Raw
QHF_00005763_MQQC_HS_EMG_551L.raw Raw
QHF_00005764_MQQC_HS_EMG_601L.raw Raw
QHF_00005765_MQQC_HS_EMG_612L.raw Raw
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