Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cold Spring Harb Perspect Med. 2013 Mar 1;3(3):a011619. doi: 10.1101/cshperspect.a011619.
During the past century, few proteins have matched erythropoietin (Epo) in capturing the imagination of physiologists, molecular biologists, and, more recently, physicians and patients. Its appeal rests on its commanding role as the premier erythroid cytokine, the elegant mechanism underlying the regulation of its gene, and its remarkable impact as a therapeutic agent, arguably the most successful drug spawned by the revolution in recombinant DNA technology. This concise review will begin with a synopsis of the colorful history of this protein, culminating in its purification and molecular cloning. It then covers in more detail the contemporary understanding of Epo's physiology as well as its structure and interaction with its receptor. A major part of this article focuses on the regulation of the Epo gene and the discovery of HIF, a transcription factor that plays a cardinal role in molecular adaptation to hypoxia. In the concluding section, a synopsis of Epo's role in disorders of red blood cell production will be followed by an assessment of the remarkable impact of Epo therapy in the treatment of anemias, as well as concerns that provide a strong impetus for the development of even safer and more effective treatment.
在过去的一个世纪中，很少有蛋白质能像促红细胞生成素 (Epo) 那样引起生理学家、分子生物学家，以及最近的医生和患者的想象。它之所以吸引人，是因为它作为主要的红细胞细胞因子，其基因调控背后的优雅机制，以及它作为治疗剂的显著影响，它可以说是重组 DNA 技术革命带来的最成功的药物。这篇简明的综述将从该蛋白质丰富多彩的历史概述开始，最终将其纯化和分子克隆。然后，它更详细地介绍了 Epo 的生理学、结构及其与受体的相互作用的现代理解。本文的一个主要部分侧重于 Epo 基因的调节以及 HIF 的发现，HIF 是一种转录因子，在分子适应缺氧方面起着至关重要的作用。在最后一节中，将概述 Epo 在红细胞生成障碍中的作用，然后评估 Epo 治疗在治疗贫血症方面的显著影响，以及为开发更安全、更有效的治疗方法提供强大动力的关注。
