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p53肿瘤抑制因子在代谢和糖尿病中的作用。

The role of the p53 tumor suppressor in metabolism and diabetes.

作者信息

Kung Che-Pei, Murphy Maureen E

机构信息

Department of Internal MedicineWashington University School of Medicine, St Louis, Missouri, USA

出版信息

J Endocrinol. 2016 Nov;231(2):R61-R75. doi: 10.1530/JOE-16-0324. Epub 2016 Sep 9.

Abstract

In the context of tumor suppression, p53 is an undisputedly critical protein. Functioning primarily as a transcription factor, p53 helps fend off the initiation and progression of tumors by inducing cell cycle arrest, senescence or programmed cell death (apoptosis) in cells at the earliest stages of precancerous development. Compelling evidence, however, suggests that p53 is involved in other aspects of human physiology, including metabolism. Indeed, recent studies suggest that p53 plays a significant role in the development of metabolic diseases, including diabetes, and further that p53's role in metabolism may also be consequential to tumor suppression. Here, we present a review of the literature on the role of p53 in metabolism, diabetes, pancreatic function, glucose homeostasis and insulin resistance. Additionally, we discuss the emerging role of genetic variation in the p53 pathway (single-nucleotide polymorphisms) on the impact of p53 in metabolic disease and diabetes. A better understanding of the relationship between p53, metabolism and diabetes may one day better inform the existing and prospective therapeutic strategies to combat this rapidly growing epidemic.

摘要

在肿瘤抑制的背景下,p53是一种毫无疑问的关键蛋白质。p53主要作为转录因子发挥作用,通过在癌前发育的最早阶段诱导细胞周期停滞、衰老或程序性细胞死亡(凋亡),帮助抵御肿瘤的发生和发展。然而,有力的证据表明,p53还参与人体生理的其他方面,包括新陈代谢。事实上,最近的研究表明,p53在包括糖尿病在内的代谢性疾病的发展中起着重要作用,而且p53在新陈代谢中的作用可能也与肿瘤抑制有关。在此,我们对有关p53在新陈代谢、糖尿病、胰腺功能、葡萄糖稳态和胰岛素抵抗方面作用的文献进行综述。此外,我们还讨论了p53途径中的基因变异(单核苷酸多态性)对p53在代谢性疾病和糖尿病中的影响所起的新作用。更好地理解p53、新陈代谢和糖尿病之间的关系,或许有朝一日能为对抗这一迅速蔓延的流行病的现有及未来治疗策略提供更充分的信息。

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The role of the p53 tumor suppressor in metabolism and diabetes.p53肿瘤抑制因子在代谢和糖尿病中的作用。
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