PXD009305

PXD009305 is an original dataset announced via ProteomeXchange.

Title	Characterisation of the Beta-Catenin cytoplasmic/nuclear interactome in leukaemia cells
Description	Canonical Wnt/B-catenin signaling is frequently dysregulated in myeloid leukemias and is implicated in leukemogenesis. Nuclear-localized β-catenin is indicative of active Wnt signaling and is frequently observed in acute myeloid leukemia (AML) patients; however, some patients exhibit little or no β-catenin nuclear-localization even where cytosolic B-catenin is abundant. Differential propensity for nuclear-localized β-catenin is also observed in cell lines. To investigate the factors mediating the nuclear-localization of B-catenin we carried out a nuclear/cytoplasmic proteomic analysis of the B-catenin interactome in myeloid leukemia cells. From this we identified hundreds of putative novel B-catenin-interactors. Comparison of interacting factors between Wnt-responsive cells (high nuclear B-catenin, K562/HEL) versus Wnt-unresponsive cells (low nuclear B-catenin, ML1) suggested the established interactor, LEF1, is a key factor mediating the nuclear-localization of B-catenin in myeloid leukemia. The relative levels of nuclear LEF1 and B-catenin were tightly correlated in both cell lines and in primary AML blasts. Furthermore, LEF1 knockdown inhibited B-catenin nuclear-localization and transcriptional activation in Wnt-responsive cells. Conversely, LEF1 overexpression was able to promote both nuclear-localization and B-catenin-dependent transcriptional responses in previously Wnt-unresponsive cells. This study is the first to present a B-catenin interactome in hematopoietic cells and reveals LEF1 as a critical regulator of canonical Wnt signaling in myeloid leukemia.
HostingRepository	PRIDE
AnnounceDate	2019-01-11
AnnouncementXML	Submission_2019-01-14_04:49:08.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: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-23 04:56:36	ID requested
1	2019-01-11 01:12:48	announced
⏵ 2	2019-01-14 04:49:09	announced	Updated publication reference for PubMed record(s): 30630973.

Morgan RG, Ridsdale J, Payne M, Heesom KJ, Wilson MC, Davidson A, Greenhough A, Davies S, Williams AC, Blair A, Waterman ML, Tonks A, Darley RL, -catenin nuclear localization in myeloid leukemia cells. Haematologica, 104(7):1365-1377(2019) [pubmed]

curator keyword: Biological

submitter keyword: Wnt Signalling, B-Catenin, Myeloid, Leukaemia, Interactome

Rhys Gareth Morgan
contact affiliation	Cellular & Molecular Medicine, University of Bristol, United Kingdom
contact email	rhys.morgan@bristol.ac.uk
lab head
Rhys Morgan
contact affiliation	University of Bristol
contact email	rhys.morgan@bristol.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009305
     1. Label: PRIDE project
     2. Name: Characterisation of the Beta-Catenin cytoplasmic/nuclear interactome in leukaemia cells