Related Experiment Video
Updated: Jun 19, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
ABL1-mediated phosphorylation promotes FOXM1-related tumorigenicity by Increasing FOXM1 stability
Qincai Dong1, Di Wang1, Caiwei Song1
1State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, 100850, Beijing, China.
ABL1 kinase stabilizes the transcription factor FOXM1 by phosphorylating it at Y575, preventing degradation. This ABL1-FOXM1 interaction promotes tumor development, suggesting ABL1 as a therapeutic target for FOXM1-driven cancers.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- FOXM1 is a transcription factor crucial for cell cycle and cancer.
- High FOXM1 expression correlates with poor prognosis but its regulation is unclear.
Purpose of the Study:
- Investigate the role of ABL1 in FOXM1 dysregulation.
- Elucidate the mechanism by which ABL1 affects FOXM1 expression and function.
- Determine the therapeutic potential of targeting the ABL1-FOXM1 axis.
Main Methods:
- Biochemical assays to study protein-protein interactions and phosphorylation.
- CRISPR/Cas9 gene editing to create mutant cell lines.
- Cellular assays to assess mitosis, colony formation, and tumor growth.
Main Results:
- ABL1 directly binds and phosphorylates FOXM1 at tyrosine residues, notably Y575.
- Phosphorylation at Y575 stabilizes FOXM1 by inhibiting its degradation via the APC/C-CDH1 complex.
- FOXM1(Y575F) mutants show reduced stability, impaired mitosis, and decreased tumor growth.
- ABL1 inhibition or FOXM1(Y575F) expression delays mitosis and inhibits tumor growth.
Conclusions:
- ABL1 kinase activity is essential for maintaining high FOXM1 levels and promoting tumor progression.
- Phosphorylation of FOXM1 at Y575 by ABL1 is a key mechanism for FOXM1 stabilization.
- Targeting ABL1 offers a potential therapeutic strategy for cancers with elevated FOXM1 expression.
More Related Videos
07:39Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
10:32Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs
Published on: December 19, 2019
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
Abnormal Proliferation
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
TGF - β Signaling Pathway
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....