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Updated: Apr 24, 2026

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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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Tracing the evolution of the p53 tetramerization domain
Andreas C Joerger1, Rainer Wilcken1, Antonina Andreeva1
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Structure (London, England : 1993)
|September 5, 2014
Summary
The p53 protein family
Area of Science:
- Evolutionary biology
- Molecular biology
- Genetics
Background:
- The p53, p63, and p73 protein family are crucial for tumor suppression and development.
- p63 and p73 possess a second helix in their tetramerization domain for stable tetramer formation, unlike human p53.
- This structural difference raises evolutionary questions regarding p53 family diversification.
Purpose of the Study:
- To investigate the evolutionary history of p53 family oligomerization domains.
- To understand the structural basis for diversification within the p53 protein family.
- To elucidate the evolutionary events shaping these domains during vertebrate evolution.
Main Methods:
- Determined the crystal structure of the zebrafish p53 tetramerization domain.
- Conducted comprehensive phylogenetic analyses of vertebrate p53 family oligomerization domains.
- Traced the evolutionary trajectory from early multicellular life to vertebrate radiation.
Main Results:
- The zebrafish p53 tetramerization domain contains a second helix, similar to p63/p73, alongside p53-like features.
- Phylogenetic analyses indicate the last common ancestor of p53 family proteins had an extended, p63/p73-like domain.
- Identified key evolutionary events influencing domain structure during vertebrate evolution.
Conclusions:
- The ancestral p53 family likely possessed a more complex tetramerization domain than currently observed in human p53.
- Evolutionary domain compaction and the transition to intrinsically disordered regions influenced human p53's interactome.
- Structural evolution of p53 family domains is linked to functional diversification and evolutionary adaptation.
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