PXD005039

PXD005039 is an original dataset announced via ProteomeXchange.

Title	Stress-induced interactome of the O-GlcNAcase by SILAC-BioID-MS/MS
Description	O-linked-β-N-acetylglucosamine (O-GlcNAc) dynamically modifies and regulates thousands of nuclear, cytoplasmic, and mitochondrial proteins. Cellular stress, including oxidative stress, results in increased O-GlcNAcylation on numerous proteins and this is thought to promote cell survival. The mechanisms by which the O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA), the enzymes that add and remove O-GlcNAc respectively, are regulated leading to oxidative stress-induced changes in O-GlcNAcylation are not fully characterized. Here, we demonstrate that oxidative stress leads to elevated O-GlcNAc levels in U2OS cells, but has little impact on the activity of OGT. In contrast, the expression and activity of OGA are enhanced. We hypothesized that protein interactors of OGA may control the local activity or substrate targeting of this enzyme, resulting in stress-induced elevations of O-GlcNAc. We utilized the BioID proximity biotinylation technique in combination with Stable Isotope Labeling of Amino Acids in Cell culture (SILAC) to define the basal and oxidative stress-dependent interactomes of OGA. Our study revealed 90 OGA-interacting partners, many of which exhibit increased binding upon oxidative stress. The associations of OGA with fatty acid synthase (FAS), filamin-A, heat shock cognate 70 kDa protein, and OGT were confirmed by co-immunoprecipitation. The pool of OGA bound to FAS demonstrates a substantial (~85%) reduction in catalytic activity, suggesting that FAS is an inhibitor of OGA. Consistent with this observation, FAS overexpression augments stress-induced O-GlcNAcylation. Together, these data suggest that O-GlcNAcylation may be one downstream effector of FAS that fine-tunes the cell’s response to stress and injury.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:32:38.076.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Groves
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; biotinylated residue; monohydroxylated residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-09-27 02:19:23	ID requested
1	2017-03-14 02:53:33	announced
⏵ 2	2024-10-22 04:32:44	announced	2024-10-22: Updated project metadata.

Groves JA, Maduka AO, O'Meally RN, Cole RN, Zachara NE, GlcNAcase during oxidative stress. J Biol Chem, 292(16):6493-6511(2017) [pubmed]

10.1074/jbc.M116.760785;

curator keyword: Biological

submitter keyword: glycosylation, mgea5, FASN, SILAC, O-GlcNAc,human, BioID

Natasha Elizabeth Zachara
contact affiliation	The Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205-2185, USA, Telephone: (410) 955-7049; Fax: (410) 955-5759
contact email	nzachara@jhmi.edu
lab head
Jennifer Groves
contact affiliation	The Johns Hopkins University School of Medicine
contact email	jgroves5@jhmi.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/2017/03/PXD005039

PRIDE project URI

• PRIDE
  1. PXD005039
     1. Label: PRIDE project
     2. Name: Stress-induced interactome of the O-GlcNAcase by SILAC-BioID-MS/MS