Phosphorylation of c-Myc at Ser62 via the protein kinase activity of acetaldehyde dehydrogenase 18A1 promotes tumor growth
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View abstract on PubMed
Summary
This summary is machine-generated.Acetaldehyde dehydrogenase 18A1 (ALDH18A1) phosphorylates and stabilizes the oncoprotein c-Myc, promoting cancer. Inhibiting this ALDH18A1-MYC interaction with thonzonium bromide (TB) shows therapeutic potential in preclinical cancer models.
Area Of Science
- Biochemistry
- Molecular Biology
- Oncology
Background
- The oncoprotein c-Myc is crucial in cancer, and its stability influences therapeutic strategies.
- Phosphorylation at Ser62 is a key mechanism that prevents c-Myc degradation, extending its half-life.
Purpose Of The Study
- To identify kinases regulating c-Myc phosphorylation at Ser62 for novel cancer interventions.
- To elucidate the role of acetaldehyde dehydrogenase 18A1 (ALDH18A1) in c-Myc regulation and cancer development.
Main Methods
- Investigated ALDH18A1's kinase activity using its γ-glutamate kinase (γ-GK) domain.
- Analyzed the feedback loop between ALDH18A1 and c-Myc expression.
- Screened FDA-approved drugs for inhibitors of the ALDH18A1-c-Myc interaction.
Main Results
- ALDH18A1 acts as a protein kinase, phosphorylating c-Myc at Ser62 and suppressing its degradation.
- A positive feedback loop between ALDH18A1 and c-Myc promotes tumor development.
- Thonzonium bromide (TB) inhibits ALDH18A1-mediated c-Myc phosphorylation and reduces tumor progression in preclinical models.
Conclusions
- ALDH18A1 is a novel kinase that stabilizes c-Myc, creating a regulatory circuit driving cancer.
- Targeting the ALDH18A1-MYC axis with inhibitors like TB offers a promising therapeutic strategy for human cancers.
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