PXD029769

PXD029769 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	SCP4-STK35/PDIK1L complex is a dual phospho-catalytic signaling dependency in acute myeloid leukemia
Description	Acute myeloid leukemia (AML) cells rely on phospho-signaling pathways to gain unlimited proliferation potential. Here, we used domain-focused CRISPR screening to identify the nuclear phosphatase SCP4 as a dependency in AML, yet this enzyme is dispensable in normal hematopoietic progenitor cells. Using CRISPR exon scanning and gene complementation assays, we show that the catalytic function of SCP4 is essential in AML. Through mass spectrometry analysis of affinity-purified complexes, we identify the kinase paralogs STK35 and PDIK1L as binding partners and substrates of the SCP4 phosphatase domain. We show that STK35 and PDIK1L function catalytically and redundantly in the same pathway as SCP4 to maintain AML proliferation and to support amino acid biosynthesis and transport. We provide evidence that SCP4 regulates STK35/PDIK1L through two distinct mechanisms: catalytic removal of inhibitory phosphorylation and by promoting kinase stability. Our findings reveal a phosphatase-kinase signaling complex that supports the pathogenesis of AML.
HostingRepository	MassIVE
AnnounceDate	2021-11-16
AnnouncementXML	Submission_2021-11-16_10:29:37.084.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Osama El Demerdash
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	unknown modification
Instrument	instrument model

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-16 10:26:51	ID requested
⏵ 1	2021-11-16 10:29:37	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: SCP4, STK35, PDIK1L, acute myeloid leukemia, phosphatase, kinase, complex, dependency

submitter keyword: SCP4, STK35, PDIK1L, acute myeloid leukemia, phosphatase, kinase, complex, dependency

Contact List

Christopher Vakoc
contact affiliation	Cold Spring Harbor Laboratory
contact email	vakoc@cshl.edu
lab head
Osama El Demerdash
contact affiliation	Cold Spring Harbor Laboratory
contact email	oeldemer@cshl.edu
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset URI

Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000088383/