Thermal stress, p53 structures and learning from elephants
Karakostis, Konstantinos (Universitat Autònoma de Barcelona)
Padariya, Monikaben (University of Gdansk (Polònia))
Thermou, Aikaterini (Hôpital St. Louis (Paris, França))
Fåhraeus, Robin (Umeå University (Suècia))
Kalathiya, Umesh (University of Gdansk (Polònia))
Vollrath, Fritz (Save the Elephants Marula Manor (Nairobi, Kenya))

Data:	2024
Resum:	As species adapt to climatic changes, temperature-dependent functions of p53 in development, metabolism and cancer will adapt as well. Structural analyses of p53 epitopes interacting in response to environmental stressors, such as heat, may uncover physiologically relevant functions of p53 in cell regulation and genomic adaptations. Here we explore the multiple p53 elephant paradigm with an experimentally validated in silico model showing that under heat stress some p53 copies escape negative regulation by the MDM2 E3 ubiquitin ligase. Multiple p53 isoforms have evolved naturally in the elephant thus presenting a unique experimental system to study the scope of p53 functions and the contribution of environmental stressors to DNA damage. We assert that fundamental insights derived from studies of a historically heat-challenged mammal will provide important insights directly relevant to human biology in the light of climate change when 'heat' may introduce novel challenges to our bodies and health.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Apoptosis ; Stress signalling ; Tumour-suppressor proteins ; Molecular modelling
Publicat a:	Cell Death Discovery, Vol. 10 (august 2024) , ISSN 2058-7716

DOI: 10.1038/s41420-024-02109-w
PMID: 39107279

5 p, 1.1 MB

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