Erythropoietin
Erythropoietin
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DOI：
10.1101/cshperspect.a011619
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发表时间：
2013-03-01
影响因子：
5.4
通讯作者：
Bunn, H. Franklin
中科院分区：
文献类型：
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作者：
Bunn, H. Franklin
在过去的一个世纪里，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注意。它的吸引力在于其作为首要红细胞细胞因子的主导作用，其基因调控的优雅机制，以及其作为治疗剂的显著影响，可以说是重组DNA技术革命催生的最成功的药物。这篇简明的综述将从这种蛋白质丰富多彩的历史的概要开始，最终在它的纯化和分子克隆。然后，它更详细地涵盖了Epo生理学的当代理解，以及它的结构和与受体的相互作用。本文的主要部分集中在Epo基因的调控和HIF的发现，HIF是一种转录因子，在分子适应缺氧中起着重要作用。在结束语部分，将简要介绍促红细胞生成素在红细胞生成障碍中的作用，然后评估促红细胞生成素治疗在治疗贫血方面的显著影响，以及为开发更安全、更有效的治疗方法提供强大动力的问题。
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.