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PXD010820

PXD010820 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleO-GlcNAcylation enhances double strand break repair, promotes cancer cell proliferation and prevents therapy-induced senescence in irradiated tumors
DescriptionThe metabolic reprogramming associated with characteristic increases in glucose and glutamine metabolism common in advanced cancer is often ascribed to answering a higher demand for metabolic intermediates required for rapid tumor cell growth. Instead, recent discoveries have pointed to an alternative role for glucose and glutamine metabolites as cofactors for chromatin modifiers and other protein post-translational modification enzymes in cancer cells. Beyond epigenetic mechanisms regulating gene expression, many chromatin modifiers also modulate DNA repair, raising the question whether cancer metabolic reprogramming may mediate resistance to genotoxic therapy and genomic instability. Our prior work had implicated N-acetyl-glucosamine (GlcNAc) formation by the hexosamine biosynthetic pathway (HBP) and resulting protein O-GlcNAcylation as a common means by which increased glucose and glutamine metabolism can drive double strand break (DSB) repair and resistance to therapy-induced senescence in cancer cells. Here, we have examined the effects of modulating O-GlcNAcylationon the DNA damage response in MCF7 human mammary carcinoma xenograft tumors. Promotingprotein O-GlcNAc modification, whether by targeting O-GlcNAcase (OGA) with shRNA or the inhibitor PUGNAc or simply treating animals with GlcNAc, protected tumor xenografts against radiation. In turn, suppressing protein O-GlcNAcylation by silencing O-GlcNActransferase (OGT) or treating animals with alloxan led to delayed DSB repair, reduced cell proliferation, and increased cell senescence in vivo. Taken together, these findings confirm critical connections between cancer metabolic reprogramming, DNA damage response, and senescence and provide a rationale to evaluate agents targeting O-GlcNAcylation in patients as a means to restore tumor sensitivity to radiotherapy.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:13:18.357.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDonald Wolfgeher
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListHex-HexNAc
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-08-20 02:19:13ID requested
12019-04-30 02:37:54announced
22019-05-02 06:47:22announcedUpdated publication reference for PubMed record(s): 30885991.
32024-10-22 04:13:19announced2024-10-22: Updated project metadata.
Publication List
Efimova EV, Appelbe OK, Ricco N, Lee SS, Liu Y, Wolfgeher DJ, Collins TN, Flor AC, Ramamurthy A, Warrington S, Bindokas VP, Kron SJ, O-GlcNAcylation Enhances Double-Strand Break Repair, Promotes Cancer Cell Proliferation, and Prevents Therapy-Induced Senescence in Irradiated Tumors. Mol Cancer Res, 17(6):1338-1350(2019) [pubmed]
10.1158/1541-7786.mcr-18-1025;
Keyword List
ProteomeXchange project tag: Glycoproteomics (B/D-HPP)
curator keyword: Biological
submitter keyword: HBP pathway, Mass Spectrometry, DNA repair, shOGA, LFQ Quantification, shOGT,O-GlcNAcylation, Chromatin Modification, Q-Exactive
Contact List
Dr. Stephen J. Kron
contact affiliationDepartment of Molecular Genetics and Cell Biology and Ludwig Center for Metastasis Research, The University of Chicago, Chicago IL
contact emailskron@uchicago.edu
lab head
Donald Wolfgeher
contact affiliationUniversity of Chicago
contact emaildonw@uchicago.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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