LEF-1 drives aberrant β-catenin nuclear localization in myeloid leukemia cells.

pubmed: wnt1 2020-06-03

Summary:

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LEF-1 drives aberrant β-catenin nuclear localization in myeloid leukemia cells.

Haematologica. 2019 07;104(7):1365-1377

Authors: 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

Abstract Canonical Wnt/β-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 nuclear β-catenin even where cytosolic β-catenin is abundant. Control of the subcellular localization of β-catenin therefore represents an additional mechanism regulating Wnt signaling in hematopoietic cells. To investigate the factors mediating the nuclear-localization of β-catenin, we carried out the first nuclear/cytoplasmic proteomic analysis of the β-catenin interactome in myeloid leukemia cells and identified putative novel β-catenin interactors. Comparison of interacting factors between Wnt-responsive cells (high nuclear β-catenin) versus Wnt-unresponsive cells (low nuclear β-catenin) suggested the transcriptional partner, LEF-1, could direct the nuclear-localization of β-catenin. The relative levels of nuclear LEF-1 and β-catenin were tightly correlated in both cell lines and in primary AML blasts. Furthermore, LEF-1 knockdown perturbed β-catenin nuclear-localization and transcriptional activation in Wnt-responsive cells. Conversely, LEF-1 overexpression was able to promote both nuclear-localization and β-catenin-dependent transcriptional responses in previously Wnt-unresponsive cells. This is the first β-catenin interactome study in hematopoietic cells and reveals LEF-1 as a mediator of nuclear β- catenin level in human myeloid leukemia.

PMID: 30630973 [PubMed - indexed for MEDLINE]

Link:

https://www.ncbi.nlm.nih.gov/pubmed/30630973?dopt=Abstract

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Exome » pubmed: wnt1

Tags:

haematologica

Authors:

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