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The Role of TP53 in Adaptation and Evolution

The TP53 gene is a major player in cancer formation, and it is considered the most important tumor suppressor gene. The p53 protein acts as a transcription factor, and it is involved in DNA repair, senescence, cell-cycle control, autophagy, and apoptosis. Beyond cancer, there is evidence that TP53 i...

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Autores principales: Voskarides, Konstantinos, Giannopoulou, Nefeli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914165/
https://www.ncbi.nlm.nih.gov/pubmed/36766853
http://dx.doi.org/10.3390/cells12030512
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author Voskarides, Konstantinos
Giannopoulou, Nefeli
author_facet Voskarides, Konstantinos
Giannopoulou, Nefeli
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description The TP53 gene is a major player in cancer formation, and it is considered the most important tumor suppressor gene. The p53 protein acts as a transcription factor, and it is involved in DNA repair, senescence, cell-cycle control, autophagy, and apoptosis. Beyond cancer, there is evidence that TP53 is associated with fertility, aging, and longevity. Additionally, more evidence exists that genetic variants in TP53 are associated with environmental adaptation. Special TP53 amino-acid residues or pathogenic TP53 mutations seem to be adaptive for animals living in hypoxic and cold environments or having been exposed to starvation, respectively. At the somatic level, it has recently been proven that multiple cancer genes, including TP53, are under positive selection in healthy human tissues. It is not clear why these driver mutations do not transform these tissues into cancerous ones. Other studies have shown that elephants have multiple TP53 copies, probably this being the reason for the very low cancer incidence in these large animals. This may explain the famous Peto’s paradox. This review discusses in detail the multilevel role of TP53 in adaptation, according to the published evidence. This role is complicated, and it extends from cells to individuals and to populations.
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spelling pubmed-99141652023-02-11 The Role of TP53 in Adaptation and Evolution Voskarides, Konstantinos Giannopoulou, Nefeli Cells Review The TP53 gene is a major player in cancer formation, and it is considered the most important tumor suppressor gene. The p53 protein acts as a transcription factor, and it is involved in DNA repair, senescence, cell-cycle control, autophagy, and apoptosis. Beyond cancer, there is evidence that TP53 is associated with fertility, aging, and longevity. Additionally, more evidence exists that genetic variants in TP53 are associated with environmental adaptation. Special TP53 amino-acid residues or pathogenic TP53 mutations seem to be adaptive for animals living in hypoxic and cold environments or having been exposed to starvation, respectively. At the somatic level, it has recently been proven that multiple cancer genes, including TP53, are under positive selection in healthy human tissues. It is not clear why these driver mutations do not transform these tissues into cancerous ones. Other studies have shown that elephants have multiple TP53 copies, probably this being the reason for the very low cancer incidence in these large animals. This may explain the famous Peto’s paradox. This review discusses in detail the multilevel role of TP53 in adaptation, according to the published evidence. This role is complicated, and it extends from cells to individuals and to populations. MDPI 2023-02-03 /pmc/articles/PMC9914165/ /pubmed/36766853 http://dx.doi.org/10.3390/cells12030512 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Voskarides, Konstantinos
Giannopoulou, Nefeli
The Role of TP53 in Adaptation and Evolution
title The Role of TP53 in Adaptation and Evolution
title_full The Role of TP53 in Adaptation and Evolution
title_fullStr The Role of TP53 in Adaptation and Evolution
title_full_unstemmed The Role of TP53 in Adaptation and Evolution
title_short The Role of TP53 in Adaptation and Evolution
title_sort role of tp53 in adaptation and evolution
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9914165/
https://www.ncbi.nlm.nih.gov/pubmed/36766853
http://dx.doi.org/10.3390/cells12030512
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