Regulation of cellular senescence via the FOXO4-p53 axis.

Regulation of cellular senescence via the FOXO4-p53 axis.
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DOI:
10.1002/1873-3468.13057
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发表时间:
2018-06
期刊:
影响因子:
3.5
通讯作者:
Madl T
Madl T
中科院分区:
生物学3区
文献类型:
--
作者:
Bourgeois B;Madl T

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Forkhead box O(FOXO)和P53蛋白是转录因子,调节不同的信号通路,控制细胞周期、细胞凋亡和代谢。在过去的十年中,FOXO和P53都被确定为衰老的关键参与者,它们的错误调控与包括癌症在内的许多疾病有关。然而,许多潜在的分子机制仍然神秘,包括FOXO和P53对衰老的调节。FOXO和P53之间似乎有几个共同的活性,包括它们在细胞衰老调节中的中心作用。在这篇综述中,我们将重点介绍FOXO和P53之间的联系的最新进展,特别是FOXO4-P53轴和FOXO4/P53在细胞衰老中的作用。此外,我们讨论了靶向FOXO4-P53相互作用以调节细胞衰老作为治疗衰老相关疾病和发病率的药物靶点的潜在策略。
Forkhead box O (FOXO) and p53 proteins are transcription factors that regulate diverse signalling pathways to control cell cycle, apoptosis and metabolism. In the last decade both FOXO and p53 have been identified as key players in aging, and their misregulation is linked to numerous diseases including cancers. However, many of the underlying molecular mechanisms remain mysterious, including regulation of ageing by FOXOs and p53. Several activities appear to be shared between FOXOs and p53, including their central role in the regulation of cellular senescence. In this review, we will focus on the recent advances on the link between FOXOs and p53, with a particular focus on the FOXO4‐p53 axis and the role of FOXO4/p53 in cellular senescence. Moreover, we discuss potential strategies for targeting the FOXO4‐p53 interaction to modulate cellular senescence as a drug target in treatment of aging‐related diseases and morbidity.
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