PXD048816-1

PXD048816 is an original dataset announced via ProteomeXchange.

Title	Spatiotemporal control of subcellular O-GlcNAc signaling using light-inducible Opto-OGT
Description	The posttranslational modification of intracellular proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is a universal regulatory mechanism in multicellular organisms driven by O-GlcNAc transferase (OGT). The complex network of signaling proteins that are activated and involved in nutrient and stress sensing pathways have made it challenging to disentangle the direct role of OGT and O-GlcNAcylation. Here, we describe Opto-OGT, an optogenetic approach that allows precise activation of OGT with light. This tool leverages on photosensitive cryptochrome fused to OGT and potentially blocks the OGT substrate site in dark state. We elucidate how activation of OGT alone can specify for distinct physiological conditions:- a short 15-min OGT activation pulse results in mTORC pathway activation and AMPK suppression, mimicking cellular signaling events activated by glucose sensing. Opto-OGT activation displays a strong temporal dependence as well - switching on OGT for 1 hour results in vice versa that represents nutrient deprivation-like response. Moreover, Opto-OGT can be customized to be activated at specific subcellular locations. As a proof-of-concept, we demonstrate downregulation of site-specific AKT phosphorylation and signaling outputs as a result of OGT recruitment towards the plasma membrane in the presence of insulin. The ability to isolate OGT as a signaling node and uncover its inherent signaling properties enables the dissection of the role of O-GlcNAcylation in whole-cell or specific compartments.
HostingRepository	jPOST
AnnounceDate	2025-01-23
AnnouncementXML	Submission_2025-01-22_07:00:05.650.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Radoslaw Sobota
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	L-methionine sulfoxide; S-carboxamidomethyl-L-cysteine; alpha-amino acetylated residue; unknown modification; unknown modification; deamidated L-asparagine; deamidated L-glutamine
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-23 18:29:50	ID requested
⏵ 1	2025-01-22 07:00:06	announced

Dataset with its publication pending

submitter keyword: O-GlcNAc signaling, spatiotemporal control, light-inducible Opto-OGT

Weiping Han and Xiaoyong Yang
lab head
Radoslaw Sobota
contact affiliation	IMCB A-STAR Singapore
dataset submitter

jPOST dataset URI

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