PXD021091-1

PXD021091 is an original dataset announced via ProteomeXchange.

Title	Quantitative Proteomics Reveals that the OGT Interactome is Remodeled in Response to Oxidative Stress
Description	The dynamic modification of specific serine and threonine residues of intracellular proteins by O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) mitigates injury and promotes cytoprotection in a variety of stress models. The O-GlcNAc transferase (OGT) and the O-GlcNAcase (OGA) are the sole enzymes that add and remove O-GlcNAc, respectively, from thousands of substrates. It remains unclear how just two enzymes can be specifically controlled to affect glycosylation of target proteins and signaling pathways both basally and in response to stress. Several lines of evidence suggest that protein interactors regulate these responses by affecting OGT and OGA activity, localization and substrate specificity. To provide insight into the mechanisms by which OGT function is controlled, we have utilized quantitative proteomics to define OGT’s basal and stress-induced interactomes. OGT and its interaction partners were immunoprecipitated from OGT wild-type, null and hydrogen peroxide treated cell lysates that had been isotopically labeled with light, medium and heavy lysine and arginine (stable isotopic labeling of amino acids in cell culture [SILAC]). In total, more than 130 proteins were found to interact with OGT, many of which change their association upon hydrogen peroxide stress. These proteins include the major OGT cleavage and glycosylation substrate, host cell factor 1, which demonstrated a time-dependent dissociation following stress. To validate less-well characterized interactors, such as glyceraldehyde 3-phosphate dehydrogenase and histone deacetylase 1, we turned to parallel reaction monitoring, which recapitulated our discovery-based SILAC approach. Although the majority of proteins identified are novel OGT interactors, 64% of them are previously characterized glycosylation targets that contain varied domain architecture and function. Together these data demonstrate that OGT interacts with unique and specific interactors in a stress-responsive manner.
HostingRepository	PanoramaPublic
AnnounceDate	2021-04-05
AnnouncementXML	Submission_2021-04-05_20:29:13.269.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Marissa Martinez
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	Carbamidomethyl
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-24 12:11:20	ID requested
⏵ 1	2021-04-05 20:29:14	announced

Martinez M, Renuse S, Kreimer S, O'Meally R, Natov P, Madugundu AK, Nirujogi RS, Tahir R, Cole R, Pandey A, Zachara NE, Quantitative Proteomics Reveals that the OGT Interactome Is Remodeled in Response to Oxidative Stress. Mol Cell Proteomics, 20():100069(2021) [pubmed]

submitter keyword: O-GlcNAc, OGT, oxidative stress

Natasha Zachara
contact affiliation	Johns Hopkins University School of Medicine
contact email	nzachara@jhmi.edu
lab head
Marissa Martinez
contact affiliation	Johns Hopkins University School of Medicine
contact email	mmartinez@foghorntx.com
dataset submitter

Panorama Public dataset URI