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The Changes in the p53 Protein across the Animal Kingdom Point to Its Involvement in Longevity

Department of Biology and Ecology, Faculty of Science, University of Ostrava, 71000 Ostrava, Czech Republic
Institute of Biophysics of the Czech Academy of Sciences, 61265 Brno, Czech Republic
Department of Physics, Faculty of Science, University of Ostrava, Chittussiho 10, 71000 Ostrava, Czech Republic
Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
Center for Hematology and Regenerative Medicine, Department of Medicine, Huddinge, Karolinska Institute, SE 171-74 Stockholm, Sweden
Author to whom correspondence should be addressed.
Academic Editors: Razmik Mirzayans and Paola Perego
Int. J. Mol. Sci. 2021, 22(16), 8512;
Received: 2 July 2021 / Revised: 29 July 2021 / Accepted: 30 July 2021 / Published: 7 August 2021
(This article belongs to the Special Issue Impacts of Molecular Structure on Nucleic Acid-Protein Interactions)
Recently, the quest for the mythical fountain of youth has produced extensive research programs that aim to extend the healthy lifespan of humans. Despite advances in our understanding of the aging process, the surprisingly extended lifespan and cancer resistance of some animal species remain unexplained. The p53 protein plays a crucial role in tumor suppression, tissue homeostasis, and aging. Long-lived, cancer-free African elephants have 20 copies of the TP53 gene, including 19 retrogenes (38 alleles), which are partially active, whereas humans possess only one copy of TP53 and have an estimated cancer mortality rate of 11–25%. The mechanism through which p53 contributes to the resolution of the Peto’s paradox in Animalia remains vague. Thus, in this work, we took advantage of the available datasets and inspected the p53 amino acid sequence of phylogenetically related organisms that show variations in their lifespans. We discovered new correlations between specific amino acid deviations in p53 and the lifespans across different animal species. We found that species with extended lifespans have certain characteristic amino acid substitutions in the p53 DNA-binding domain that alter its function, as depicted from the Phenotypic Annotation of p53 Mutations, using the PROVEAN tool or SWISS-MODEL workflow. In addition, the loop 2 region of the human p53 DNA-binding domain was identified as the longest region that was associated with longevity. The 3D model revealed variations in the loop 2 structure in long-lived species when compared with human p53. Our findings show a direct association between specific amino acid residues in p53 protein, changes in p53 functionality, and the extended animal lifespan, and further highlight the importance of p53 protein in aging.
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Keywords: p53; aging; longevity; comparative analysis; protein sequence p53; aging; longevity; comparative analysis; protein sequence
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MDPI and ACS Style

Bartas, M.; Brázda, V.; Volná, A.; Červeň, J.; Pečinka, P.; Zawacka-Pankau, J.E. The Changes in the p53 Protein across the Animal Kingdom Point to Its Involvement in Longevity. Int. J. Mol. Sci. 2021, 22, 8512.

AMA Style

Bartas M, Brázda V, Volná A, Červeň J, Pečinka P, Zawacka-Pankau JE. The Changes in the p53 Protein across the Animal Kingdom Point to Its Involvement in Longevity. International Journal of Molecular Sciences. 2021; 22(16):8512.

Chicago/Turabian Style

Bartas, Martin, Václav Brázda, Adriana Volná, Jiří Červeň, Petr Pečinka, and Joanna E. Zawacka-Pankau. 2021. "The Changes in the p53 Protein across the Animal Kingdom Point to Its Involvement in Longevity" International Journal of Molecular Sciences 22, no. 16: 8512.

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