Using Mice to Examine p53 Functions in Cancer, Aging, and Longevity
Using Mice to Examine p53 Functions in Cancer, Aging, and Longevity
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DOI：
10.1101/cshperspect.a001081
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发表时间：
2009-12-01
影响因子：
7.2
通讯作者：
Donehower, Lawrence A.
中科院分区：
文献类型：
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作者：
Donehower, Lawrence A.
p53肿瘤抑制因子是一个多方面的转录因子，可响应多种应激，包括DNA损伤和异常癌基因信号。在激活时，p53通过启动细胞周期阻滞、衰老（终末细胞周期阻滞）或凋亡来阻止癌细胞的出现。尽管p53在抑制癌症、保证寿命方面的作用已经得到了很好的证实，但最近主要来自基因工程小鼠模型的研究表明，p53可能调节寿命和衰老。在某些情况下，p53活性的改变可能会延长寿命，而在其他情况下，它似乎会抑制寿命并加速衰老表型。在这里，我们讨论了如何使用基因工程小鼠模型来探索p53在癌症抑制中的抗增殖功能，以及改变衰老表型的小鼠模型如何揭示p53如何影响衰老过程。
The p53 tumor suppressor is a multifaceted transcription factor that responds to a diverse array of stresses that include DNA damage and aberrant oncogene signaling. On activation, p53 prevents the emergence of cancer cells by initiating cell cycle arrest, senescence ( terminal cell cycle arrest), or apoptosis. Although its role in assuring longevity by suppressing cancer is well established, recent studies obtained largely from genetically engineered mouse models suggest that p53 may regulate longevity and aging. In some contexts, it appears that altered p53 activity may enhance longevity, and in others, it appears to suppress longevity and accelerate aging phenotypes. Here, we discuss how genetically engineered mouse models have been used to explore antiproliferative functions of p53 in cancer suppression and how mouse models with altered aging phenotypes have shed light on how p53 might influence the aging process.