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Assessment of Thermal Stability of Mutant p53 Proteins via Differential Scanning Fluorimetry

The p53 protein is a transcription factor that preserves the integrity of the genome. The TP53 gene has inactivating mutations in about 50% of all human cancers. Some missense mutations lead to decreased thermal stability in the p53 protein, its unfolding and aggregation under physiological conditio...

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Autores principales: Khadiullina, Raniya, Mirgayazova, Regina, Davletshin, Damir, Khusainova, Elvina, Chasov, Vitaly, Bulatov, Emil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9862671/
https://www.ncbi.nlm.nih.gov/pubmed/36675980
http://dx.doi.org/10.3390/life13010031
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author Khadiullina, Raniya
Mirgayazova, Regina
Davletshin, Damir
Khusainova, Elvina
Chasov, Vitaly
Bulatov, Emil
author_facet Khadiullina, Raniya
Mirgayazova, Regina
Davletshin, Damir
Khusainova, Elvina
Chasov, Vitaly
Bulatov, Emil
author_sort Khadiullina, Raniya
collection PubMed
description The p53 protein is a transcription factor that preserves the integrity of the genome. The TP53 gene has inactivating mutations in about 50% of all human cancers. Some missense mutations lead to decreased thermal stability in the p53 protein, its unfolding and aggregation under physiological conditions. A general understanding of the impact of point mutations on the stability and conformation of mutant p53 is essential for the design and development of small molecules that target specific p53 mutations. In this work, we determined the thermostability properties of some of the most common mutant forms of the p53 protein—p53(R273H), p53(R248Q), p53(R248W) and p53(Y220C)—that are often considered as attractive therapeutic targets. The results showed that these missense mutations lead to destabilization of the p53 protein and a decrease in its melting temperature.
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spelling pubmed-98626712023-01-22 Assessment of Thermal Stability of Mutant p53 Proteins via Differential Scanning Fluorimetry Khadiullina, Raniya Mirgayazova, Regina Davletshin, Damir Khusainova, Elvina Chasov, Vitaly Bulatov, Emil Life (Basel) Communication The p53 protein is a transcription factor that preserves the integrity of the genome. The TP53 gene has inactivating mutations in about 50% of all human cancers. Some missense mutations lead to decreased thermal stability in the p53 protein, its unfolding and aggregation under physiological conditions. A general understanding of the impact of point mutations on the stability and conformation of mutant p53 is essential for the design and development of small molecules that target specific p53 mutations. In this work, we determined the thermostability properties of some of the most common mutant forms of the p53 protein—p53(R273H), p53(R248Q), p53(R248W) and p53(Y220C)—that are often considered as attractive therapeutic targets. The results showed that these missense mutations lead to destabilization of the p53 protein and a decrease in its melting temperature. MDPI 2022-12-22 /pmc/articles/PMC9862671/ /pubmed/36675980 http://dx.doi.org/10.3390/life13010031 Text en © 2022 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 Communication
Khadiullina, Raniya
Mirgayazova, Regina
Davletshin, Damir
Khusainova, Elvina
Chasov, Vitaly
Bulatov, Emil
Assessment of Thermal Stability of Mutant p53 Proteins via Differential Scanning Fluorimetry
title Assessment of Thermal Stability of Mutant p53 Proteins via Differential Scanning Fluorimetry
title_full Assessment of Thermal Stability of Mutant p53 Proteins via Differential Scanning Fluorimetry
title_fullStr Assessment of Thermal Stability of Mutant p53 Proteins via Differential Scanning Fluorimetry
title_full_unstemmed Assessment of Thermal Stability of Mutant p53 Proteins via Differential Scanning Fluorimetry
title_short Assessment of Thermal Stability of Mutant p53 Proteins via Differential Scanning Fluorimetry
title_sort assessment of thermal stability of mutant p53 proteins via differential scanning fluorimetry
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9862671/
https://www.ncbi.nlm.nih.gov/pubmed/36675980
http://dx.doi.org/10.3390/life13010031
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