PXD035686 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2023-01-09 |
AnnouncementXML | Submission_2023-01-09_06:15:00.854.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | ChristinaWoo |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
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. |
Publication List
Keyword List
submitter keyword: O-GlcNAcylation |
Contact List
christinawoo |
contact affiliation | harvard University |
contact email | cwoo@harvard.edu |
lab head | |
ChristinaWoo |
contact affiliation | Harvard University |
contact email | cwoo@chemistry.harvard.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035686
- Label: PRIDE project
- Name: Small molecule-mediated O-GlcNAcase activation for precise control of O-GlcNAcylation in live cells