Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Antioxid Redox Signal. 2011 Sep 15;15(6):1739-48. doi: 10.1089/ars.2010.3650. Epub 2011 Apr 14.
p53 regulates the cell cycle and deoxyribonucleic acid (DNA) repair pathways as part of its unequivocally important function to maintain genomic stability. Intriguingly, recent studies show that p53 can also transactivate genes involved in coordinating the two major pathways of energy generation to promote aerobic metabolism, but how this serves to maintain genomic stability is less clear. In an attempt to understand the biology, this review presents human epidemiologic data on the inverse relationship between aerobic capacity and cancer incidence that appears to be mirrored by the impact of p53 on aerobic capacity in mouse models. The review summarizes mechanisms by which p53 regulates mitochondrial respiration and proposes how this might contribute to maintaining genomic stability. Although disparate in nature, the data taken together suggest that the promotion of aerobic metabolism by p53 serves as an important tumor suppressor activity and may provide insights for cancer prevention strategies in the future.
p53 通过调节细胞周期和脱氧核糖核酸（DNA）修复途径来维持基因组稳定性，这是其至关重要的功能之一。有趣的是，最近的研究表明，p53 还可以转录激活参与协调两种主要能量生成途径的基因，以促进有氧代谢，但这如何有助于维持基因组稳定性尚不清楚。为了理解生物学，本综述介绍了关于有氧能力与癌症发病率之间呈反比关系的人类流行病学数据，这似乎与 p53 对小鼠模型有氧能力的影响相呼应。该综述总结了 p53 调节线粒体呼吸的机制，并提出了这可能有助于维持基因组稳定性的方式。尽管性质不同，但这些数据表明，p53 促进有氧代谢是一种重要的肿瘤抑制活性，可能为未来的癌症预防策略提供思路。
