Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, Austria.
BioTechMed, Graz, Austria.
FEBS Lett. 2018 Jun;592(12):2083-2097. doi: 10.1002/1873-3468.13057. Epub 2018 May 25.
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.
叉头框 O（FOXO）和 p53 蛋白是转录因子，可调节多种信号通路以控制细胞周期、细胞凋亡和代谢。在过去的十年中，FOXO 和 p53 已被确定为衰老的关键参与者，其失调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 似乎有一些共同的活动，包括它们在细胞衰老调控中的核心作用。在这篇综述中，我们将重点介绍 FOXO 和 p53 之间联系的最新进展，特别关注 FOXO4-p53 轴以及 FOXO4/p53 在细胞衰老中的作用。此外，我们还讨论了靶向 FOXO4-p53 相互作用以调节细胞衰老作为治疗与衰老相关疾病和发病率的药物靶点的潜在策略。
