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PXD051532

PXD051532 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIdentification of WNK1 as a therapeutic target to suppress IgH/MYC expression in multiple myeloma
DescriptionMultiple myeloma (MM) remains a challenging hematological malignancy demanding innovative therapeutic strategies. Targeting MYC, the notorious yet traditionally undruggable oncogene, presents an appealing avenue. Here, using a genome-scale CRISPR/Cas9 screen, we identify the WNK lysine deficient protein kinase 1 (WNK1) as a regulator of MYC expression in MM cells. Genetic and pharmacological inhibition of WNK1 reduces MYC expression, and further, disrupts the MYC-dependent transcriptional program. Mechanistically, WNK1 inhibition attenuates the activity of the immunoglobulin heavy chain (IgH) enhancer, thus reducing MYC transcription when this locus is translocated near the MYC locus. WNK1 inhibition profoundly impacts MM cell behaviors, leading to growth inhibition, cell cycle arrest, senescence, and apoptosis. Importantly, the WNK inhibitor WNK463 synergizes with various anti-MM compounds, and inhibits MM growth in primary patient samples as well as xenograft mouse models. Collectively, our study uncovers WNK1 as a potential therapeutic target in MM.
HostingRepositoryiProX
AnnounceDate2024-04-18
AnnouncementXMLSubmission_2024-04-18_22:51:28.548.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYaohui He
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion ETD
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-04-17 19:14:22ID requested
12024-04-18 22:51:28announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Multiple myeloma, IgH translocation, MYC, CRISPR screen, WNK1
Contact List
Wen Liu
contact affiliationXiamen University
contact emailw2liu@xmu.edu.cn
lab head
Yaohui He
contact affiliationXiamen University
contact emailyhhe@xmu.edu.cn
dataset submitter
Full Dataset Link List
iProX dataset URI