PXD014373

PXD014373 is an original dataset announced via ProteomeXchange.

Title	Proteomic response of yeast cells to 2-deoxyglucose exposure (0.2%, 2.5h)
Description	Cancer cells display an altered metabolism with increased glycolysis and glucose uptake. Anti-cancer strategies targeting glycolysis through metabolic inhibitors have been considered. The glucose analog 2-deoxyglucose (2DG) is imported into cells and after phosphorylation becomes 2DG-6-phosphate, a toxic by-product that inhibits glycolysis. 2DG has other cellular effects and can induce resistance. Using yeast as a model, we performed an unbiased, mass-spectrometry-based approach to probe the cellular effects of 2DG on the proteome and study resistance mechanisms. We found that two 2DG-6-phosphate phosphatases, Dog1 and Dog2, were induced upon exposure to 2DG and participated in 2DG detoxication. 2DG induced Dog2 by activating several signaling pathways, such as the MAPK (the p38 ortholog Hog1)-based stress-responsive pathway, the unfolded protein response (UPR) triggered by 2DG-induced ER stress, and the MAPK (Slt2)-based cell wall integrity (CWI) pathway. Thus, 2DG-induced interference with cellular signaling rewired the expression of these endogenous phosphatases to promote 2DG resistance. Consequently, loss of the UPR or CWI pathways led to 2DG hypersensitivity. In contrast, DOG2 was transcriptionally repressed by glucose availability through the inhibition of the Snf1/AMPK pathway, and glucose-repression mutants were 2DG-resistant. The characterization and genome resequencing of spontaneous 2DG-resistant mutants revealed that DOG2 overexpression was a common strategy to achieve 2DG resistance. A human Dog2 homolog, HDHD1, also displays 2DG-6-phosphate phosphatase activity in vitro, and its overexpression conferred 2DG resistance in HeLa cells, suggesting potential interference with chemotherapies involving 2DG.
HostingRepository	PRIDE
AnnounceDate	2019-09-09
AnnouncementXML	Submission_2019-09-09_08:40:37.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sebastien LEON
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	ubiquitinylated lysine; phosphorylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-06-25 01:46:28	ID requested
⏵ 1	2019-09-09 08:40:38	announced

Defenouill, è, re Q, Verraes A, Laussel C, Friedrich A, Schacherer J, L, é, on S, The induction of HAD-like phosphatases by multiple signaling pathways confers resistance to the metabolic inhibitor 2-deoxyglucose. Sci Signal, 12(597):(2019) [pubmed]

submitter keyword: Saccharomyces cerevisiae, 2-deoxyglucose

Sebastien LEON
contact affiliation	Institut Jacques Monod, CNRS/Université de Paris, Paris-France
contact email	sebastien.leon@ijm.fr
lab head
Sebastien LEON
contact affiliation	Institut Jacques Monod
contact email	sebastien.leon@ijm.fr
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/2019/09/PXD014373

PRIDE project URI

• PRIDE
  1. PXD014373
     1. Label: PRIDE project
     2. Name: Proteomic response of yeast cells to 2-deoxyglucose exposure (0.2%, 2.5h)