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Reduced structural rigidity of MDMX protein enhances binding to TP53 mRNA
Martina Kucerikova1,2, Ondrej Bonczek1, Vanesa Olivares-Illana3
1RECAMO, Masaryk Memorial Cancer Institute, Brno, 602 00, Czechia.
Bioscience Reports
|November 13, 2025
Summary
MDMX protein binds to TP53 mRNA, enhancing p53 production. This interaction involves the MDMX RING domain and is influenced by the entire protein structure, crucial for DNA damage response.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- MDM2 and MDMX are key negative regulators of p53.
- Under DNA damage, MDM2 and MDMX become positive regulators of p53.
- MDMX facilitates MDM2 binding to TP53 mRNA, boosting p53 production.
Purpose of the Study:
- To elucidate the specific features of the MDMX-RNA interaction.
- To characterize the binding of MDMX to TP53 mRNA.
- To understand how different MDMX domains contribute to RNA binding.
Main Methods:
- Protein construct analysis
- Hydrogen-deuterium exchange mass spectrometry (HDX-MS)
- RNA binding assays under varying salt and pH conditions
Main Results:
- MDMX RING domain is involved in TP53 mRNA binding.
- The entire MDMX protein, particularly the C-terminal domain, participates in RNA interaction.
- Protein structural destabilization (e.g., via EDTA or TCEP) enhances RNA binding.
Conclusions:
- MDMX-TP53 mRNA interaction is complex, with the RING domain and whole protein acting as a scaffold.
- Understanding this interaction provides insights into p53 stabilization and activation under DNA damage.
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