PXD042838

PXD042838 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-09 01:42:03	ID requested
⏵ 1	2024-05-30 07:19:47	announced

Dataset with its publication pending

submitter keyword: MITF, Palbociclib,O-GlcNAc

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

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PRIDE project URI

• PRIDE
  1. PXD042838
     1. Label: PRIDE project
     2. Name: O-GlcNAcylation promotes Palbociclib resistance in breast cancer by regulating MITF nuclear translocation