哺乳动物胞外 5′-核苷酸酶（CD73）的优雅复杂性。
The elegant complexity of mammalian ecto-5'-nucleotidase (CD73).
机构信息
Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
出版信息
Trends Cell Biol. 2021 Oct;31(10):829-842. doi: 10.1016/j.tcb.2021.05.008. Epub 2021 Jun 8.
Abstract
Purinergic signaling is a fundamental mechanism used by all cells to control their internal activities and interact with the environment. A key component of the purinergic system, the enzyme ecto-5'-nucleotidase (CD73) catalyzes the last step in the extracellular metabolism of ATP to form adenosine. Efforts to harness the therapeutic potential of endogenous adenosine in cancer have culminated in the ongoing clinical development of multiple CD73-targeting antibodies and small-molecule inhibitors. However, recent studies are painting an increasingly complex picture of CD73 mRNA and protein regulation and function in cellular homeostasis, physiological adaptation, and disease development. This review discusses the latest conceptual and methodological advances that are helping to unravel the complexity of this important enzyme that was identified nearly 90 years ago.
摘要
嘌呤能信号转导是所有细胞用来控制其内部活动并与环境相互作用的基本机制。嘌呤能系统的一个关键组成部分，酶外核苷酸酶（CD73）催化 ATP 在外周代谢中的最后一步，形成腺苷。利用内源性腺苷在癌症中的治疗潜力的努力已经促成了多种 CD73 靶向抗体和小分子抑制剂的临床开发。然而，最近的研究越来越清楚地描绘了 CD73 mRNA 和蛋白在细胞内稳态、生理适应和疾病发展中的调节和功能。这篇综述讨论了最新的概念和方法学进展，这些进展有助于揭示这一重要酶的复杂性，该酶在近 90 年前被发现。
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Purinergic Signal. 2021 Mar;17(1):117-125. doi: 10.1007/s11302-020-09755-6. Epub 2020 Dec 17.
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Biochem Pharmacol. 2021 May;187:114322. doi: 10.1016/j.bcp.2020.114322. Epub 2020 Nov 6.
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