PXD042838 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | O-GlcNAcylation promotes Palbociclib resistance in breast cancer by regulating MITF nuclear translocation |
Description | Cyclin-dependent kinases 4 and 6 (CDK4/6) are essential drivers of the cell cycle and are also critical for the initiation and progression of diverse malignancies. Pharmacological inhibitors targeting CDK4/6 have demonstrated significant activity against various tumor types such as breast cancer. However, resistance to CDK4/6 inhibitors (CDK4/6i) (such as palbociclib) remains an immense obstacle in clinical and the underlying mechanisms have not been fully understood. Using quantitative high-throughput combinational screen (qHTCS) and genomic sequencing, we report that the Microphthalmia-associated transcription factor (MITF), was significantly elevated in palbociclib-resistance cells. Inhibition of MITF can enhance the therapeutic efficacy of Palbociclib and surmount Palbociclib resistance both in vitro and in vivo. Mechanistically, we found that O-GlcNAc transferase (OGT) modifies MITF with O-GlcNAcylation at Serine 49 (Ser49) within its nuclear localization signal (NLS), thereby promoting MITF binding to importin α/ β and facilitating its nuclear transportation, which is crucial in regulating senescence. |
HostingRepository | PRIDE |
AnnounceDate | 2024-05-30 |
AnnouncementXML | Submission_2024-05-30_07:19:46.987.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | YI ZHANG |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | complex glycosylation |
Instrument | LCQ Classic |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-06-09 01:42:03 | ID requested | |
⏵ 1 | 2024-05-30 07:19:47 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: MITF, Palbociclib,O-GlcNAc |
Contact List
Wenge Zhu |
contact affiliation | George Washington University |
contact email | wz6812@gwu.edu |
lab head | |
YI ZHANG |
contact affiliation | The George Washington University |
contact email | scholarzy@gwu.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042838
- Label: PRIDE project
- Name: O-GlcNAcylation promotes Palbociclib resistance in breast cancer by regulating MITF nuclear translocation