p53 异构体：细胞命运决定的关键调节因子。
p53 Isoforms: Key Regulators of the Cell Fate Decision.
作者信息
Joruiz Sebastien M, Bourdon Jean-Christophe
机构信息
Dundee Cancer Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, United Kingdom.
出版信息
Cold Spring Harb Perspect Med. 2016 Aug 1;6(8):a026039. doi: 10.1101/cshperspect.a026039.
Abstract
It is poorly understood how a single protein, p53, can be responsive to so many stress signals and orchestrates very diverse cell responses to maintain/restore cell/tissue functions. The uncovering that TP53 gene physiologically expresses, in a tissue-dependent manner, several p53 splice variants (isoforms) provides an explanation to its pleiotropic biological activities. Here, we summarize a decade of research on p53 isoforms. The clinical studies and the diverse cellular and animal models of p53 isoforms (zebrafish, Drosophila, and mouse) lead us to realize that a p53-mediated cell response is, in fact, the sum of the intrinsic activities of the coexpressed p53 isoforms and that unbalancing expression of different p53 isoforms leads to cancer, premature aging, (neuro)degenerative diseases, inflammation, embryo malformations, or defects in tissue regeneration. Cracking the p53 isoforms' code is, thus, a necessary step to improve cancer treatment. It also opens new exciting perspectives in tissue regeneration.
摘要
目前人们对单个蛋白质p53如何能对如此多的应激信号作出反应，并协调非常多样的细胞反应以维持/恢复细胞/组织功能了解甚少。TP53基因以组织依赖的方式生理性表达多种p53剪接变体（异构体）这一发现，为其多效性生物学活性提供了解释。在此，我们总结了十年来关于p53异构体的研究。p53异构体的临床研究以及多种细胞和动物模型（斑马鱼、果蝇和小鼠）使我们认识到，p53介导的细胞反应实际上是共表达的p53异构体内在活性的总和，不同p53异构体表达失衡会导致癌症、早衰、（神经）退行性疾病、炎症、胚胎畸形或组织再生缺陷。因此，破解p53异构体的密码是改善癌症治疗的必要步骤。它也为组织再生开辟了新的令人兴奋的前景。
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p53 isoform Δ113p53/Δ133p53 promotes DNA double-strand break repair to protect cell from death and senescence in response to DNA damage.p53 异构体Δ113p53/Δ133p53促进DNA双链断裂修复，以保护细胞免受DNA损伤诱导的死亡和衰老。
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