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Updated: May 7, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar stress
Katherine E Sloan1, Markus T Bohnsack, Nicholas J Watkins
1ICaMB, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Centre for Biochemistry and Molecular Cell Biology, Institute for Molecular Biology, Medical Faculty, Georg-August University, 37073 Goettingen, Germany.
Abstract:
Several proto-oncogenes and tumor suppressors regulate the production of ribosomes. Ribosome biogenesis is a major consumer of cellular energy, and defects result in p53 activation via repression of mouse double minute 2 (MDM2) homolog by the ribosomal proteins RPL5 and RPL11. Here, we report that RPL5 and RPL11 regulate p53 from the context of a ribosomal subcomplex, the 5S ribonucleoprotein particle (RNP). We provide evidence that the third component of this complex, the 5S rRNA, is critical for p53 regulation. In addition, we show that the 5S RNP is essential for the activation of p53 by p14(ARF), a protein that is activated by oncogene overexpression. Our data show that the abundance of the 5S RNP, and therefore p53 levels, is determined by factors regulating 5S complex formation and ribosome integration, including the tumor suppressor PICT1. The 5S RNP therefore emerges as the critical coordinator of signaling pathways that couple cell proliferation with ribosome production.
Insights
The 5S ribonucleoprotein particle (RNP) regulates p53 activation, linking cell proliferation to ribosome production. This ribosomal subcomplex, including 5S rRNA, RPL5, and RPL11, is crucial for tumor suppressor activity.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Proto-oncogenes and tumor suppressors control ribosome production.
- Ribosome biogenesis is energy-intensive, and defects trigger p53 activation.
- Ribosomal proteins RPL5 and RPL11 repress MDM2 homolog, activating p53.
Purpose of the Study:
- Investigate the role of the 5S ribonucleoprotein particle (RNP) in p53 regulation.
- Determine the significance of 5S rRNA within the 5S RNP complex.
- Elucidate the connection between 5S RNP, p14(ARF), and p53 activation.
Main Methods:
- Analysis of ribosomal subcomplexes.
- Investigation of protein-RNA interactions.
- Study of p53 activation pathways.
Main Results:
- RPL5 and RPL11 regulate p53 from within the 5S RNP.
- 5S rRNA is essential for p53 regulation by the 5S RNP.
- The 5S RNP is critical for p14(ARF)-mediated p53 activation.
- PICT1 influences 5S RNP abundance and subsequent p53 levels.
Conclusions:
- The 5S RNP acts as a key regulator of p53.
- This complex links ribosome production with cell proliferation control.
- The 5S RNP is a critical signaling hub in cancer-related pathways.
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