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Updated: Jun 4, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
The tumor suppressor p53 connects ribosome biogenesis to cell cycle control: a double-edged sword
Michael Hölzel1,2, Kaspar Burger1, Bastian Mühl1
1Department of Molecular Epigenetics, Center of Integrated Protein Science (CIPSM), Helmholtz Center Munich, Munich, Germany.
Abstract:
Since its first description more than 30 years ago p53 has become a paradigm for a protein with versatile functions. P53 sensitizes a large variety of genetic alterations and has been entitled the guardian of the genome. Stabilization of p53 upon DNA damage is accompanied by a complex pattern of modifications, which ascertain the cellular response either in the direction of a reversible or irreversible cell cycle arrest or programmed cell death. More recently it became evident that p53 also responds to non-genotoxic cell stress, in particular if ribosome biogenesis is affected.
Insights
The p53 protein, known as the guardian of the genome, responds to DNA damage and non-genotoxic stress. Its stabilization involves modifications that direct cellular responses like cell cycle arrest or cell death, especially when ribosome biogenesis is impacted.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The p53 protein, described over 30 years ago, is a key regulator of cellular responses.
- P53 is recognized as the 'guardian of the genome' due to its role in sensing genetic alterations.
- Cellular stress, particularly DNA damage, triggers p53 stabilization through complex post-translational modifications.
Purpose of the Study:
- To elucidate the multifaceted roles of the p53 protein in cellular regulation.
- To understand the mechanisms by which p53 responds to various forms of cellular stress.
- To investigate the involvement of p53 in non-genotoxic stress, specifically related to ribosome biogenesis.
Main Methods:
- Literature review of p53 research over the past three decades.
- Analysis of studies detailing p53 post-translational modifications upon DNA damage.
- Examination of recent findings on p53's response to non-genotoxic stressors affecting ribosome biogenesis.
Main Results:
- P53 exhibits versatile functions, acting as a critical sensor for genetic instability.
- DNA damage induces p53 stabilization, leading to modifications that dictate cell cycle arrest or apoptosis.
- Emerging evidence shows p53 also responds to non-genotoxic stress, notably when ribosome biogenesis is compromised.
Conclusions:
- P53 plays a pivotal role in maintaining genomic integrity and orchestrating cellular fate.
- The modification patterns of p53 are crucial for determining the outcome of cellular stress responses.
- The newly identified role of p53 in ribosome biogenesis-related stress expands our understanding of its regulatory network.
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