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Deciphering the significance of p53 mutant proteins

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2024

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Trends in Cell Biology. Elsevier. ISSN 0962-8924. eISSN 1879-3088. Verfügbar unter: doi: 10.1016/j.tcb.2024.06.003

Zusammenfassung

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.

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570 Biowissenschaften, Biologie

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ISO 690BUTERA, Alessio, Ivano AMELIO, 2024. Deciphering the significance of p53 mutant proteins. In: Trends in Cell Biology. Elsevier. ISSN 0962-8924. eISSN 1879-3088. Verfügbar unter: doi: 10.1016/j.tcb.2024.06.003
BibTex
@article{Butera2024Decip-70395,
  year={2024},
  doi={10.1016/j.tcb.2024.06.003},
  title={Deciphering the significance of p53 mutant proteins},
  issn={0962-8924},
  journal={Trends in Cell Biology},
  author={Butera, Alessio and Amelio, Ivano}
}
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    <dcterms: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.</dcterms:abstract>
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