The Changes in the p53 Protein across the Animal Kingdom Point to Its Involvement in Longevity
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61988987%3A17310%2F21%3AA2202AMQ" target="_blank" >RIV/61988987:17310/21:A2202AMQ - isvavai.cz</a>
Alternative codes found
RIV/68081707:_____/21:00554786
Result on the web
<a href="https://www.mdpi.com/1422-0067/22/16/8512" target="_blank" >https://www.mdpi.com/1422-0067/22/16/8512</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/ijms22168512" target="_blank" >10.3390/ijms22168512</a>
Alternative languages
Result language
angličtina
Original language name
The Changes in the p53 Protein across the Animal Kingdom Point to Its Involvement in Longevity
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/GA18-15548S" target="_blank" >GA18-15548S: Comparative study of DNA interacting properties of the tumor suppressor p53 protein isoforms</a><br>
Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
1422-0067
e-ISSN
1422-0067
Volume of the periodical
22
Issue of the periodical within the volume
16
Country of publishing house
CH - SWITZERLAND
Number of pages
23
Pages from-to
1-23
UT code for WoS article
000690510300001
EID of the result in the Scopus database
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