PXD010820 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | O-GlcNAcylation enhances double strand break repair, promotes cancer cell proliferation and prevents therapy-induced senescence in irradiated tumors |
Description | The 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:13:18.357.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Donald Wolfgeher |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | Hex-HexNAc |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-08-20 02:19:13 | ID requested | |
1 | 2019-04-30 02:37:54 | announced | |
2 | 2019-05-02 06:47:22 | announced | Updated publication reference for PubMed record(s): 30885991. |
⏵ 3 | 2024-10-22 04:13:19 | announced | 2024-10-22: 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 affiliation | Department of Molecular Genetics and Cell Biology and Ludwig Center for Metastasis Research, The University of Chicago, Chicago IL |
contact email | skron@uchicago.edu |
lab head | |
Donald Wolfgeher |
contact affiliation | University of Chicago |
contact email | donw@uchicago.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD010820
- Label: PRIDE project
- Name: O-GlcNAcylation enhances double strand break repair, promotes cancer cell proliferation and prevents therapy-induced senescence in irradiated tumors