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Thermal stress, p53 structures and learning from elephants.

Konstantinos Karakostis^1,2, Monikaben Padariya³, Aikaterini Thermou⁴

¹Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. konstantinos.karakostis@gmail.com.

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Summary

Elephant p53 isoforms offer insights into heat stress adaptation. Under heat, some p53 copies evade MDM2 regulation, revealing potential genomic adaptation mechanisms relevant to human health and climate change.

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Area of Science:

Evolutionary biology
Molecular biology
Genomics

Background:

Species adapt to climate change, influencing temperature-dependent biological functions.
The tumor suppressor protein p53 plays roles in development, metabolism, and cancer.
Environmental stressors like heat can impact cellular regulation and genomic stability.

Purpose of the Study:

To explore the "multiple p53 elephant paradigm" using an in silico model.
To investigate how heat stress affects p53 regulation by MDM2.
To understand the role of environmental stressors in DNA damage and genomic adaptation.

Main Methods:

Utilized an experimentally validated in silico model.
Analyzed structural epitopes of p53 in response to heat stress.
Leveraged the unique system of multiple p53 isoforms naturally evolved in elephants.

Main Results:

Demonstrated that under heat stress, some p53 copies escape negative regulation by MDM2.
Identified potential physiologically relevant functions of p53 in cell regulation.
Highlighted the contribution of environmental stressors to DNA damage and adaptation.

Conclusions:

Fundamental insights from heat-adapted mammals like elephants are relevant to human biology.
Climate change-induced heat may introduce novel challenges to human health.
Studying elephant p53 provides a unique system to understand p53 functions and environmental adaptation.