Deciphering the significance of p53 mutant proteins.

IF 13 1区 生物学 Q1 CELL BIOLOGY Trends in Cell Biology Pub Date : 2024-07-02 DOI:10.1016/j.tcb.2024.06.003
Alessio Butera, Ivano Amelio
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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.

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解密 p53 突变蛋白的意义。
p53 基因的突变损害了其作为基因组完整性守护者的作用,主要产生错义 p53 突变蛋白。长期以来,功能增益假说一直认为这些突变蛋白具有新的致癌特性;然而,最近的研究对这一观点提出了质疑,表明针对这些突变体可能不会影响癌细胞的健康。越来越多的证据表明,肿瘤发生涉及驱动突变和细胞状态之间的合作性相互作用,并受到发育阶段、外部损伤和组织损伤的影响。p53突变体的行为和特性始终受环境影响而改变。本文旨在对有关 p53 突变体在癌症生物学中的作用的不断演变的证据进行平衡的总结,同时考虑采用其他框架来解读 p53 突变体在其生理环境中的复杂性。
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来源期刊
Trends in Cell Biology
Trends in Cell Biology 生物-细胞生物学
CiteScore
32.00
自引率
0.50%
发文量
160
审稿时长
61 days
期刊介绍: Trends in Cell Biology stands as a prominent review journal in molecular and cell biology. Monthly review articles track the current breadth and depth of research in cell biology, reporting on emerging developments and integrating various methods, disciplines, and principles. Beyond Reviews, the journal features Opinion articles that follow trends, offer innovative ideas, and provide insights into the implications of new developments, suggesting future directions. All articles are commissioned from leading scientists and undergo rigorous peer-review to ensure balance and accuracy.
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