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Updated: Jun 25, 2025
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Entosis implicates a new role for P53 in microcephaly pathogenesis, beyond apoptosis
Noelle A Sterling1,2, Seo-Hee Cho3, Seonhee Kim1
1Shriners Hospitals Pediatric Research Center, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA.
Abstract:
Entosis, a form of cell cannibalism, is a newly discovered pathogenic mechanism leading to the development of small brains, termed microcephaly, in which P53 activation was found to play a major role. Microcephaly with entosis, found in Pals1 mutant mice, displays P53 activation that promotes entosis and apoptotic cell death. This previously unappreciated pathogenic mechanism represents a novel cellular dynamic in dividing cortical progenitors which is responsible for cell loss. To date, various recent models of microcephaly have bolstered the importance of P53 activation in cell death leading to microcephaly. P53 activation caused by mitotic delay or DNA damage manifests apoptotic cell death which can be suppressed by P53 removal in these animal models. Such genetic studies attest P53 activation as quality control meant to eliminate genomically unfit cells with minimal involvement in the actual function of microcephaly associated genes. In this review, we summarize the known role of P53 activation in a variety of microcephaly models and introduce a novel mechanism wherein entotic cell cannibalism in neural progenitors is triggered by P53 activation.
Insights
P53 activation triggers entosis, a form of cell cannibalism, leading to microcephaly (small brain) by causing cell loss in developing neural progenitors. This newly identified mechanism highlights P53
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Microcephaly is a condition characterized by a small brain.
- P53 activation is implicated in various microcephaly models, primarily through apoptosis.
- Entosis, a form of cell cannibalism, is a newly recognized pathogenic mechanism.
Purpose of the Study:
- To review the role of P53 activation in microcephaly.
- To introduce entosis as a novel pathogenic mechanism in microcephaly development.
- To explore the link between P53 activation and entosis in neural progenitors.
Main Methods:
- Review of existing literature on P53 activation and microcephaly models.
- Analysis of findings in Pals1 mutant mice exhibiting microcephaly with entosis.
- Examination of cellular dynamics in dividing cortical progenitors.
Main Results:
- P53 activation promotes both entosis and apoptotic cell death in Pals1 mutant mice.
- Entosis represents a novel cellular dynamic contributing to cell loss in developing brains.
- P53 activation acts as a quality control mechanism eliminating unfit cells.
Conclusions:
- P53 activation triggers entosis, a novel mechanism contributing to microcephaly.
- Entotic cell cannibalism in neural progenitors is a significant factor in microcephaly pathogenesis.
- Understanding this pathway offers new insights into brain development disorders.
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