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PXD041902

PXD041902 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleWNK1 signalling regulates amino acid transport and mTORC1 activity to sustain AML growth
DescriptionThe lack of curative therapies for acute myeloid leukaemia (AML) remains an ongoing challenge despite recent advances in the understanding of the molecular basis of the disease. Here we identify the WNK1-OXSR1/STK39 pathway as a previously uncharacterised dependency in AML. We show that genetic depletion and pharmacological inhibition of WNK1 or its downstream phosphorylation targets OXSR1 and STK39 strongly reduce cell proliferation and induce apoptosis in leukemic cells in vitro and in vivo. Furthermore, we show that the WNK1-OXSR1/STK39 pathway controls mTOR signalling via regulating amino acid uptake through a mechanism involving the phosphorylation of amino acid transporters, such as SLC38A2. Our results demonstrate a critical role of the WNK1-OXSR1/STK39 pathway in regulating amino acid uptake and in AML maintenance. Moreover, our mode of action studies suggests that WNK1 and OXSR1/STK39 inhibitors could be effective in a broad range of cancer types.
HostingRepositoryPRIDE
AnnounceDate2025-06-02
AnnouncementXMLSubmission_2025-06-01_16:24:08.786.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPavel Shliaha
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-05-01 04:44:17ID requested
12025-06-01 16:24:09announced
Publication List
Duan S, Agger K, Messling JE, Nishimura K, Han X, Pe, ñ, a-R, ø, mer I, Shliaha P, Damhofer H, Douglas M, Kohli M, Pal A, Asad Y, Van Dyke A, Reilly R, K, ö, chl R, Tybulewicz VLJ, Hendrickson RC, Raynaud FI, Gallipoli P, Poulogiannis G, Helin K, WNK1 signalling regulates amino acid transport and mTORC1 activity to sustain acute myeloid leukaemia growth. Nat Commun, 16(1):4920(2025) [pubmed]
10.1038/s41467-025-59969-8;
Keyword List
submitter keyword: WNK1, phosphoproteomics, AML, mTOR
Contact List
Ronald Hendrickson
contact affiliationMemorial Sloan Kettering Cancer Center
contact emailhendricr@mskcc.org
lab head
Pavel Shliaha
contact affiliationMRC London Institute of Medical Sciences proteomics and metabolomics core
contact emailpavel.shliaha@gmail.com
dataset submitter
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Dataset FTP location
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