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.
摘要：
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。功能获得假说长期以来一直表明这些突变蛋白获得了新的致癌特性；然而，最近的研究挑战了这一概念，这表明靶向这些突变体可能不会影响癌细胞的适应性。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相互作用，受发育阶段的影响，外部侮辱,和组织损伤。始终如一，p53突变体的行为和性质被上下文改变。本文旨在提供有关p53突变体在癌症生物学中的贡献的不断发展的证据的平衡总结，同时考虑替代框架来破译p53突变体在其生理环境中的复杂性。
