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Deciphering the significance of p53 mutant proteins.

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Title: Deciphering the significance of p53 mutant proteins.
Authors: Butera A; Chair of Systems Toxicology, University of Konstanz, Konstanz, Germany., Amelio I; Chair of Systems Toxicology, University of Konstanz, Konstanz, Germany. Electronic address: ivano.amelio@uni-konstanz.de.
Source: Trends in cell biology [Trends Cell Biol] 2025 Mar; Vol. 35 (3), pp. 258-268. Date of Electronic Publication: 2024 Jul 02.
Publication Type: Journal Article; Review
Language: English
Journal Info: Publisher: Elsevier Science Publishers Country of Publication: England NLM ID: 9200566 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3088 (Electronic) Linking ISSN: 09628924 NLM ISO Abbreviation: Trends Cell Biol Subsets: MEDLINE
Imprint Name(s): Original Publication: Cambridge, UK : Elsevier Science Publishers, c1991-
MeSH Terms: Tumor Suppressor Protein p53*/genetics , Tumor Suppressor Protein p53*/metabolism , Mutation*/genetics , Neoplasms*/genetics , Neoplasms*/metabolism , Neoplasms*/pathology , Mutant Proteins*/genetics , Mutant Proteins*/metabolism, Humans ; Animals
Abstract: Mutations in the p53 gene compromise its role as guardian of genomic integrity, yielding predominantly missense p53 mutant proteins. The gain-of-function hypothesis has long suggested that these mutant proteins acquire new oncogenic properties; however, recent studies challenge this notion, indicating that targeting these mutants may not impact the fitness of cancer cells. Mounting evidence indicates that tumorigenesis involves a cooperative interplay between driver mutations and cellular state, influenced by developmental stage, external insults, and tissue damage. Consistently, the behavior and properties of p53 mutants are altered by the context. This article aims to provide a balanced summary of the evolving evidence regarding the contribution of p53 mutants in the biology of cancer while contemplating alternative frameworks to decipher the complexity of p53 mutants within their physiological contexts.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Competing Interests: Declaration of interests The authors declare that they have no competing interests.
Comments: Erratum in: Trends Cell Biol. 2026 Apr 1:S0962-8924(26)00002-4. doi: 10.1016/j.tcb.2026.01.002.. (PMID: 41927354)
Contributed Indexing: Keywords: cancer; context-dependent; dominant-negative; gain-of-function; microenvironment
Substance Nomenclature: 0 (Tumor Suppressor Protein p53)
0 (Mutant Proteins)
Entry Date(s): Date Created: 20240703 Date Completed: 20250422 Latest Revision: 20260402
Update Code: 20260403
DOI: 10.1016/j.tcb.2024.06.003
PMID: 38960851
Database: MEDLINE
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  Data: Deciphering the significance of p53 mutant proteins.
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  Data: <searchLink fieldCode="AU" term="%22Butera+A%22">Butera A</searchLink>; Chair of Systems Toxicology, University of Konstanz, Konstanz, Germany.<br /><searchLink fieldCode="AU" term="%22Amelio+I%22">Amelio I</searchLink>; Chair of Systems Toxicology, University of Konstanz, Konstanz, Germany. Electronic address: ivano.amelio@uni-konstanz.de.
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  Data: <searchLink fieldCode="JN" term="%229200566%22">Trends in cell biology</searchLink> [Trends Cell Biol] 2025 Mar; Vol. 35 (3), pp. 258-268. <i>Date of Electronic Publication: </i>2024 Jul 02.
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  Data: Journal Article; Review
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Elsevier+Science+Publishers%22">Elsevier Science Publishers </searchLink><i>Country of Publication: </i>England <i>NLM ID: </i>9200566 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1879-3088 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2209628924%22">09628924 </searchLink><i>NLM ISO Abbreviation: </i>Trends Cell Biol <i>Subsets: </i>MEDLINE
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  Data: <i>Original Publication</i>: Cambridge, UK : Elsevier Science Publishers, c1991-
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  Data: <searchLink fieldCode="MM" term="%22Tumor+Suppressor+Protein+p53%22">Tumor Suppressor Protein p53*</searchLink>/<searchLink fieldCode="MM" term="%22Tumor+Suppressor+Protein+p53+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Tumor+Suppressor+Protein+p53%22">Tumor Suppressor Protein p53*</searchLink>/<searchLink fieldCode="MM" term="%22Tumor+Suppressor+Protein+p53+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Mutation%22">Mutation*</searchLink>/<searchLink fieldCode="MM" term="%22Mutation+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Neoplasms%22">Neoplasms*</searchLink>/<searchLink fieldCode="MM" term="%22Neoplasms+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Neoplasms%22">Neoplasms*</searchLink>/<searchLink fieldCode="MM" term="%22Neoplasms+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Neoplasms%22">Neoplasms*</searchLink>/<searchLink fieldCode="MM" term="%22Neoplasms+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Mutant+Proteins%22">Mutant Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Mutant+Proteins+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Mutant+Proteins%22">Mutant Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Mutant+Proteins+metabolism%22">metabolism</searchLink><br /><searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Mutations in the p53 gene compromise its role as guardian of genomic integrity, yielding predominantly missense p53 mutant proteins. The gain-of-function hypothesis has long suggested that these mutant proteins acquire new oncogenic properties; however, recent studies challenge this notion, indicating that targeting these mutants may not impact the fitness of cancer cells. Mounting evidence indicates that tumorigenesis involves a cooperative interplay between driver mutations and cellular state, influenced by developmental stage, external insults, and tissue damage. Consistently, the behavior and properties of p53 mutants are altered by the context. This article aims to provide a balanced summary of the evolving evidence regarding the contribution of p53 mutants in the biology of cancer while contemplating alternative frameworks to decipher the complexity of p53 mutants within their physiological contexts.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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  Data: Declaration of interests The authors declare that they have no competing interests.
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  Data: Erratum in: Trends Cell Biol. 2026 Apr 1:S0962-8924(26)00002-4. doi: 10.1016/j.tcb.2026.01.002.. (PMID: <searchLink fieldCode="PM" term="%2241927354%22">41927354)</searchLink>
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  Data: <i>Keywords: </i>cancer; context-dependent; dominant-negative; gain-of-function; microenvironment
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  Data: 0 (Tumor Suppressor Protein p53)<br />0 (Mutant Proteins)
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        Value: 10.1016/j.tcb.2024.06.003
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        Text: English
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      – SubjectFull: Mutant Proteins genetics
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