PXD035686

PXD035686 is an original dataset announced via ProteomeXchange.

Title	Small molecule-mediated O-GlcNAcase activation for precise control of O-GlcNAcylation in live cells
Description	O-GlcNAc is a nutritionally and metabolically relevant post-translational modification on thousands of nucleocytoplas-mic proteins. O-GlcNAcylation level dynamically responds to environmental cues in temporal and spatial dimensions, leading to discrete signaling transductions and physiological effects. Spatiotemporal regulation of O-GlcNAcylation level is essential for O-GlcNAc functional interrogation and manipulation of cell behaviors for desired outcomes, which is yet challenging owing to limited approaches. Here we achieved spatiotemporal O-GlcNAc reduction in live cells by designing a 4-hydroxytamoxifen (4-HT)-triggered O-GlcNAcase (OGA) activation strategy. After rational engineering and optimiza-tion, OGA variants bearing an intein located to different subcellular regions were generated and validated, whose deglyco-sidase activity can be turned on by 4-HT in a time- and dose-dependent manner. Finally, we demonstrated the dual func-tionality of 4-HT on breast cancer cells expressing the engineered OGA, which accelerated cell death with a lower dosage and thus mitigated the likelihood of acquiring drug resistance. Altogether, our strategy facilitates the precise regulation and functional understandings of O-GlcNAcylation in live cells.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:57:20.468.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christina Woo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-01 09:28:04	ID requested
1	2023-01-09 06:15:01	announced
⏵ 2	2023-11-14 08:57:20	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: O-GlcNAcylation

christina woo
contact affiliation	harvard University
contact email	cwoo@harvard.edu
lab head
Christina Woo
contact affiliation	Harvard University
contact email	cwoo@chemistry.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035686
     1. Label: PRIDE project
     2. Name: Small molecule-mediated O-GlcNAcase activation for precise control of O-GlcNAcylation in live cells