Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
Am J Pathol. 2020 Aug;190(8):1584-1595. doi: 10.1016/j.ajpath.2020.04.003. Epub 2020 Apr 24.
Maintaining oxygen homeostasis is a most basic cellular process for adapting physiological oxygen variations, and its abnormality typically leads to various disorders in the human body. The key molecules of the oxygen-sensing system include the transcriptional regulator hypoxia-inducible factor (HIF), which controls a wide range of oxygen responsive target genes (eg, EPO and VEGF), certain members of the oxygen/2-oxoglutarate-dependent dioxygenase family, including the HIF proline hydroxylase (PHD, alias EGLN), and an E3 ubiquitin ligase component for HIF destruction called von Hippel-Lindau. In this review, we summarize the physiological role and highlight the pathologic function for each protein of the oxygen-sensing system. A better understanding of their molecular mechanisms of action will help uncover novel therapeutic targets and develop more effective treatment approaches for related human diseases, including cancer.
维持氧平衡是适应生理氧变化的最基本的细胞过程，其异常通常会导致人体出现各种疾病。氧感应系统的关键分子包括转录调节因子缺氧诱导因子 (HIF)，它控制着广泛的氧反应靶基因（例如 EPO 和 VEGF），某些氧/2-酮戊二酸依赖性双氧酶家族成员，包括 HIF 脯氨酸羟化酶 (PHD，别名 EGLN)，以及用于 HIF 降解的 E3 泛素连接酶成分称为 von Hippel-Lindau。在这篇综述中，我们总结了氧感应系统中每种蛋白质的生理作用，并强调了其病理功能。更好地了解它们的作用机制将有助于发现新的治疗靶点，并为相关人类疾病（包括癌症）开发更有效的治疗方法。
