PXD051532-1

PXD051532 is an original dataset announced via ProteomeXchange.

Title	Identification of WNK1 as a therapeutic target to suppress IgH/MYC expression in multiple myeloma
Description	Multiple 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.
HostingRepository	iProX
AnnounceDate	2024-04-18
AnnouncementXML	Submission_2024-04-18_22:51:28.548.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yaohui He
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion ETD

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-17 19:14:22	ID requested
⏵ 1	2024-04-18 22:51:28	announced

Dataset with its publication pending

submitter keyword: Multiple myeloma, IgH translocation, MYC, CRISPR screen, WNK1

Wen Liu
contact affiliation	Xiamen University
contact email	w2liu@xmu.edu.cn
lab head
Yaohui He
contact affiliation	Xiamen University
contact email	yhhe@xmu.edu.cn
dataset submitter

iProX dataset URI