PXD070891

PXD070891 is an original dataset announced via ProteomeXchange.

Title	Assessment of global peptide abundance in TOE1 depleted myeloid leukaemia cells
Description	Acute myeloid leukaemia (AML) is an aggressive haematological malignancy characterised by the clonal proliferation of myeloid progenitor cells in the bone marrow and peripheral blood. Dysregulation of the Wnt/β-catenin pathway has been implicated in the establishment and maintenance of leukaemic stem cells in AML, where higher expression of β-catenin promotes clonogenic capacity, drug resistance and inferior survival. The finding that low levels of Wnt signalling are necessary to maintain normal haematopoiesis makes β-catenin an attractive therapeutic target, however drug design has been hampered by a poor understanding of its molecular interactions in leukaemia cells. To address this, we previously characterised the β-catenin interactome in myeloid cells and identified a plethora of novel interacting proteins. One such validated interactor was Target of EGR1 (TOE1), a 510-amino acid member of the Asp-Glu-Asp-Asp (DEDD) family of deadenylases with previously uncharacterised function in haematopoietic cells. The β-catenin:TOE1 interaction was detected in the nuclear and cytosolic compartments of myeloid cell lines and primary AML samples, and β-catenin knockdown via short hairpin RNA (shRNA) was found to promote the cytosolic stabilisation of TOE1. Furthermore, TOE1 levels were found to be overexpressed in primary AML blasts versus normal cord-blood derived CD34+ haematopoietic stem and progenitor cells (HSPCs), suggesting that TOE1 levels may be dysregulated in leukaemia. TOE1 depletion using shRNA abrogated Wnt signalling capacity (TCF/LEF activity) through suppression of the Wnt transcription factor lymphoid enhancing factor 1 (LEF-1), likely via post-transcriptional mechanisms. TOE1 shRNA further suppressed the proliferation and survival of myeloid leukaemia cell lines (HEL and OCI-AML2) and primary human CD34+ HSPC, however this could not be fully explained through LEF-1 alone, since OCI-AML2 do not express LEF-1. Therefore, to explore a more unifying mechanism mediating the growth promoting phenotype of TOE1 we performed tandem mass tag (TMT)-labelling coupled to mass spectrometry analysis in TOE1 deficient HEL and OCI-AML2 cells. From this analysis we identified validated p21 (RAC1) activated kinase 2 (PAK2) as a consistently downregulated target across both cell lines, and demonstrated PAK2 knockdown alone was sufficient to reduce the proliferation (but not survival) of AML cell lines. Finally, expression of ectopic PAK2 was able to partially rescue the suppressed proliferation mediated by TOE1 depletion in myeloid cell lines, and primary human CD34+ HSPC. In summary, these data reveal TOE1 as novel interacting partner for β-catenin in haematological cells capable of modulating Wnt signalling output via LEF-1, and as a novel mediator of growth and survival in human HSPC and AML cells partly through PAK2 regulation.
HostingRepository	PRIDE
AnnounceDate	2026-04-29
AnnouncementXML	Submission_2026-04-29_04:24:41.255.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rhys Morgan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-18 08:13:05	ID requested
⏵ 1	2026-04-29 04:24:42	announced

Park H, Sevim O, Wagstaff M, Goff A, Palmer DA, Kim B, Heesom K, Blair A, Newbury SF, Morgan EL, Towler BP, Chevassut TJ, Morgan RG, -catenin interacting protein regulating the proliferation of hematopoietic cells through PAK2 modulation. Stem Cell Reports, 21(5):102894(2026) [pubmed]

10.1016/j.stemcr.2026.102894;

submitter keyword: AML

HEL

OCI-AML2

TOE1

HSPC

human

shRNA

leukaemia

Rhys G Morgan
contact affiliation	Faculty of Science, Engineering & Medicine, School of Life Sciences, University of Sussex, United Kingdom
contact email	rhys.morgan@sussex.ac.uk
lab head
Rhys Morgan
contact affiliation	University of Sussex
contact email	rhys.morgan@sussex.ac.uk
dataset submitter

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://ftp.pride.ebi.ac.uk/pride/data/archive/2026/04/PXD070891

PRIDE project URI

• PRIDE
  1. PXD070891
     1. Label: PRIDE project
     2. Name: Assessment of global peptide abundance in TOE1 depleted myeloid leukaemia cells