PXD010820

PXD010820 is an original dataset announced via ProteomeXchange.

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

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.

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;

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

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

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/2019/04/PXD010820

PRIDE project URI

• PRIDE
  1. PXD010820
     1. Label: PRIDE project
     2. Name: O-GlcNAcylation enhances double strand break repair, promotes cancer cell proliferation and prevents therapy-induced senescence in irradiated tumors