ArticleThe EMBO journal2007
Bcr-Abl stabilizes beta-catenin in chronic myeloid leukemia through its tyrosine phosphorylation.
Article in The EMBO journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 212 citations in OpenAlex.
- Statins exert the pleiotropic effects through small GTP-binding protein dissociation stimulator upregulation with a resultant Rac1 degradation.Arteriosclerosis, thrombosis, and vascular biology · 2013Trial
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- Quantitative high-throughput screening identifies small-molecule modulators of Wnt/β-catenin signaling.Frontiers in pharmacology · 2026Article
- Nuclear β-catenin: molecular regulation, challenges and therapeutic opportunities.Cell communication and signaling : CCS · 2025Review
- β-Catenin/c-Myc Axis Modulates Autophagy Response to Different Ammonia Concentrations.Advanced biology · 2025Article
- DeepKinome: quantitative prediction of kinase binding affinity by a compound using deep learning based regression model.Frontiers in molecular biosciences · 2025Article
- Article
- A conserved ZFX/WNT3 axis modulates the growth and imatinib response of chronic myeloid leukemia stem/progenitor cells.Cellular & molecular biology letters · 2023Article
- Visinin-like 1, a novel target gene of the Wnt/β-catenin signaling pathway, is involved in apoptosis resistance in colorectal cancer.Cancer medicine · 2023Article
- A streamlined tandem tip-based workflow for sensitive nanoscale phosphoproteomics.Communications biology · 2023Article
- PTMint database of experimentally verified PTM regulation on protein-protein interaction.Bioinformatics (Oxford, England) · 2023Article
- Review
- Targeting β-catenin in acute myeloid leukaemia: past, present, and future perspectives.Bioscience reports · 2022Review
- BCR-ABL1 Tyrosine Kinase Complex Signaling Transduction: Challenges to Overcome Resistance in Chronic Myeloid Leukemia.Pharmaceutics · 2022Review
- Phosphorylation-Dependent Regulation of WNT/Beta-Catenin Signaling.Frontiers in oncology · 2022Review
- Chronic myeloid leukemia stem cells: targeting therapeutic implications.Stem cell research & therapy · 2021Review
- Leukemia Stem Cells as a Potential Target to Achieve Therapy-Free Remission in Chronic Myeloid Leukemia.Cancers · 2021Review
- Statins Enhance the Molecular Response in Chronic Myeloid Leukemia when Combined with Tyrosine Kinase Inhibitors.Cancers · 2021Article
- An MST4-pβ-CateninAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Urokinase-type plasminogen activator-mediated crosstalk between N-cadherin and β-catenin promotes wound healing.Journal of cell science · 2021Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Self-renewal of Bcr-Abl(+) chronic myeloid leukemia (CML) cells is sustained by a nuclear activated serine/threonine-(S/T) unphosphorylated beta-catenin. Although beta-catenin can be tyrosine (Y)-phosphorylated, the occurrence and biological relevance of this covalent modification in Bcr-Abl-associated leukemogenesis is unknown. Here we show that Bcr-Abl levels control the degree of beta-catenin protein stabilization by affecting its Y/S/T-phospho content in CML cells. Bcr-Abl physically interacts with beta-catenin, and its oncogenic tyrosine kinase activity is required to phosphorylate beta-catenin at Y86 and Y654 residues. This Y-phospho beta-catenin binds to the TCF4 transcription factor, thus representing a transcriptionally active pool. Imatinib, a Bcr-Abl antagonist, impairs the beta-catenin/TCF-related transcription causing a rapid cytosolic retention of Y-unphosphorylated beta-catenin, which presents an increased binding affinity for the Axin/GSK3beta complex. Although Bcr-Abl does not affect GSK3beta autophosphorylation, it prevents, through its effect on beta-catenin Y phosphorylation, Axin/GSK3beta binding to beta-catenin and its subsequent S/T phosphorylation. Silencing of beta-catenin by small interfering RNA inhibited proliferation and clonogenicity of Bcr-Abl(+) CML cells, in synergism with Imatinib. These findings indicate the Bcr-Abl triggered Y phosphorylation of beta-catenin as a new mechanism responsible for its protein stabilization and nuclear signalling activation in CML.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.