Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1784875147204755456 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9862671 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT khadiullinaraniya assessmentofthermalstabilityofmutantp53proteinsviadifferentialscanningfluorimetry AT mirgayazovaregina assessmentofthermalstabilityofmutantp53proteinsviadifferentialscanningfluorimetry AT davletshindamir assessmentofthermalstabilityofmutantp53proteinsviadifferentialscanningfluorimetry AT khusainovaelvina assessmentofthermalstabilityofmutantp53proteinsviadifferentialscanningfluorimetry AT chasovvitaly assessmentofthermalstabilityofmutantp53proteinsviadifferentialscanningfluorimetry AT bulatovemil assessmentofthermalstabilityofmutantp53proteinsviadifferentialscanningfluorimetry |