Redox Sensitive Cysteine Residues as Crucial Regulators of Wild-Type and Mutant p53 Isoforms

The wild-type protein p53 plays a key role in preventing the formation of neoplasms by controlling cell growth. However, in more than a half of all cancers, the <i>TP53</i> gene has missense mutations that appear during tumorigenesis. In most cases, the mutated gene encodes a full-length...

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Autores principales:	Elena Butturini, Giovanna Butera, Raffaella Pacchiana, Alessandra Carcereri de Prati, Sofia Mariotto, Massimo Donadelli
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cancer p53 mutant p53 redox oxidative stress post-translational modifications Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8f6cb1b86bad4870b96b979da2adcf92
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spelling	oai:doaj.org-article:8f6cb1b86bad4870b96b979da2adcf922021-11-25T17:11:59ZRedox Sensitive Cysteine Residues as Crucial Regulators of Wild-Type and Mutant p53 Isoforms10.3390/cells101131492073-4409https://doaj.org/article/8f6cb1b86bad4870b96b979da2adcf922021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3149https://doaj.org/toc/2073-4409The wild-type protein p53 plays a key role in preventing the formation of neoplasms by controlling cell growth. However, in more than a half of all cancers, the <i>TP53</i> gene has missense mutations that appear during tumorigenesis. In most cases, the mutated gene encodes a full-length protein with the substitution of a single amino acid, resulting in structural and functional changes and acquiring an oncogenic role. This dual role of the wild-type protein and the mutated isoforms is also evident in the regulation of the redox state of the cell, with antioxidant and prooxidant functions, respectively. In this review, we introduce a new concept of the p53 protein by discussing its sensitivity to the cellular redox state. In particular, we focus on the discussion of structural and functional changes following post-translational modifications of redox-sensitive cysteine residues, which are also responsible for interacting with zinc ions for proper structural folding. We will also discuss therapeutic opportunities using small molecules targeting cysteines capable of modifying the structure and function of the p53 mutant isoforms in view of possible anticancer therapies for patients possessing the mutation in the <i>TP53</i> gene.Elena ButturiniGiovanna ButeraRaffaella PacchianaAlessandra Carcereri de PratiSofia MariottoMassimo DonadelliMDPI AGarticlecancerp53mutant p53redoxoxidative stresspost-translational modificationsBiology (General)QH301-705.5ENCells, Vol 10, Iss 3149, p 3149 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer p53 mutant p53 redox oxidative stress post-translational modifications Biology (General) QH301-705.5
spellingShingle	cancer p53 mutant p53 redox oxidative stress post-translational modifications Biology (General) QH301-705.5 Elena Butturini Giovanna Butera Raffaella Pacchiana Alessandra Carcereri de Prati Sofia Mariotto Massimo Donadelli Redox Sensitive Cysteine Residues as Crucial Regulators of Wild-Type and Mutant p53 Isoforms
description	The wild-type protein p53 plays a key role in preventing the formation of neoplasms by controlling cell growth. However, in more than a half of all cancers, the <i>TP53</i> gene has missense mutations that appear during tumorigenesis. In most cases, the mutated gene encodes a full-length protein with the substitution of a single amino acid, resulting in structural and functional changes and acquiring an oncogenic role. This dual role of the wild-type protein and the mutated isoforms is also evident in the regulation of the redox state of the cell, with antioxidant and prooxidant functions, respectively. In this review, we introduce a new concept of the p53 protein by discussing its sensitivity to the cellular redox state. In particular, we focus on the discussion of structural and functional changes following post-translational modifications of redox-sensitive cysteine residues, which are also responsible for interacting with zinc ions for proper structural folding. We will also discuss therapeutic opportunities using small molecules targeting cysteines capable of modifying the structure and function of the p53 mutant isoforms in view of possible anticancer therapies for patients possessing the mutation in the <i>TP53</i> gene.
format	article
author	Elena Butturini Giovanna Butera Raffaella Pacchiana Alessandra Carcereri de Prati Sofia Mariotto Massimo Donadelli
author_facet	Elena Butturini Giovanna Butera Raffaella Pacchiana Alessandra Carcereri de Prati Sofia Mariotto Massimo Donadelli
author_sort	Elena Butturini
title	Redox Sensitive Cysteine Residues as Crucial Regulators of Wild-Type and Mutant p53 Isoforms
title_short	Redox Sensitive Cysteine Residues as Crucial Regulators of Wild-Type and Mutant p53 Isoforms
title_full	Redox Sensitive Cysteine Residues as Crucial Regulators of Wild-Type and Mutant p53 Isoforms
title_fullStr	Redox Sensitive Cysteine Residues as Crucial Regulators of Wild-Type and Mutant p53 Isoforms
title_full_unstemmed	Redox Sensitive Cysteine Residues as Crucial Regulators of Wild-Type and Mutant p53 Isoforms
title_sort	redox sensitive cysteine residues as crucial regulators of wild-type and mutant p53 isoforms
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8f6cb1b86bad4870b96b979da2adcf92
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Redox Sensitive Cysteine Residues as Crucial Regulators of Wild-Type and Mutant p53 Isoforms

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