Institute of Biochemistry, University of Kiel, Germany.
Institute of Biochemistry, University of Kiel, Germany.
Biochim Biophys Acta Mol Cell Res. 2017 Nov;1864(11 Pt B):2059-2070. doi: 10.1016/j.bbamcr.2017.07.001. Epub 2017 Jul 11.
The disintegrin metalloprotease ADAM17 has been a matter of intense studies aiming to unravel structure, function and regulation of protease expression, maturation and activity. In this review, we summarize data on the physiological role of ADAM17 in health and disease. Here we provide an overview of ADAM17 substrates, mouse models of ADAM17-deficiencies and discuss recent findings of ADAM17 function in the immune system and central nervous system as well as in cancer. Whereas ADAM17 function in EGF-R-, in Interleukin-6 (IL-6)- and in TNFα-biology has been shown to play a decisive role in regulation of the immune system as well as cancer development, the role of ADAM17 in the central nervous system and neurodegeneration still remains elusive. We show ADAM17 expression in human dopaminergic neurons derived from induced pluripotent stem cells and we discuss how this state-of-the-art technology can be further exploited to study the function of this important protease in the brain and other tissues. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.
去整合素金属蛋白酶 ADAM17 一直是研究的热点，旨在阐明蛋白酶表达、成熟和活性的结构、功能和调节。在这篇综述中，我们总结了 ADAM17 在健康和疾病中的生理作用的数据。在这里，我们提供了 ADAM17 底物、ADAM17 缺陷的小鼠模型的概述，并讨论了 ADAM17 功能在免疫系统和中枢神经系统以及癌症中的最新发现。虽然 ADAM17 在表皮生长因子受体 (EGF-R)、白细胞介素 6 (IL-6) 和肿瘤坏死因子-α (TNFα) 生物学中的功能已被证明在免疫系统和癌症发展的调节中起着决定性的作用，但 ADAM17 在中枢神经系统和神经退行性变中的作用仍然难以捉摸。我们在源自诱导多能干细胞的人类多巴胺能神经元中显示 ADAM17 的表达，并讨论如何进一步利用这项最先进的技术来研究这种重要蛋白酶在大脑和其他组织中的功能。本文是由 Stefan Rose-John 编辑的题为“蛋白水解作用作为病理生理学中的调节事件”的特刊的一部分。
