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The MDM2 oncoprotein binds specifically to RNA through its RING finger domain
B Elenbaas1, M Dobbelstein, J Roth
1Department of Molecular Biology, Princeton University, NJ 08544-1014, USA.
Molecular Medicine (Cambridge, Mass.)
|July 1, 1996
Summary
The MDM2 protein binds to specific RNA sequences and structures, suggesting a role in translational regulation. This binding occurs through the RING finger domain and is independent of L5 protein interaction.
Area of Science:
- Molecular Biology
- Cancer Research
- RNA Biology
Background:
- The MDM2 gene exhibits transforming activity when overexpressed and is amplified in various human tumors.
- MDM2 protein contributes to transformation by binding and inactivating the p53 tumor suppressor.
- MDM2 protein interacts with L5 ribosomal protein and 5S ribosomal RNA, potentially forming part of a ribosomal complex.
Purpose of the Study:
- To characterize the RNA-binding activity of the MDM2 protein.
- To identify specific RNA ligands that bind with high affinity to human MDM2 (HDM2).
Main Methods:
- RNA homopolymer binding assays were employed.
- A SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure was utilized.
- RNA ligands were selected, amplified, and sequenced.
Main Results:
- MDM2 protein efficiently binds to poly(G) homopolyribonucleotides but not others.
- Specific RNA binding is mediated by the RING finger domain of MDM2.
- A G446S substitution in the RING finger domain abolished specific RNA binding, independent of L5 protein interaction.
Conclusions:
- MDM2 binds to the L5/5S ribosomal ribonucleoprotein particle.
- MDM2 demonstrates the ability to bind specific RNA sequences or structures.
- These findings suggest a role for MDM2 in cellular translational regulation.