The EGLN-HIF O(2)-Sensing System: Multiple Inputs and Feedbacks.

The EGLN-HIF O(2)-Sensing System: Multiple Inputs and Feedbacks.
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DOI:
10.1016/j.molcel.2017.06.002
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发表时间:
2017-06-15
期刊:
影响因子:
16
通讯作者:
Kaelin WG Jr
Kaelin WG Jr
中科院分区:
生物学1区
文献类型:
--
作者:
Ivan M;Kaelin WG Jr

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EGLN(也称为PHD)脯氨酸羟基酶及其典型的靶标--缺氧诱导因子α亚单位,代表了后生动物使用的古老氧气监测机制的核心。在这篇综述中,我们重点介绍了在理解EGLN酶和HIF异构体的重叠和特定作用方面的最新进展,并讨论了基于最近发现的非编码RNA的反馈环如何为缺氧反应带来额外的复杂性。基于发现的EGLN上游和下游的新的相互作用,一个将氧感应功能与代谢和信号通路联系起来的集成网络正在逐渐出现,具有广泛的治疗意义。
The EGLN (also called PHD) prolyl hydroxylase enzymes and their canonical targets, the HIFα subunits, represent the core of an ancient oxygen-monitoring machinery used by metazoans. In this review we highlight recent progress in understanding the overlapping versus specific roles of EGLN enzymes and HIF isoforms and discuss how feedback loops based on recently identified noncoding RNAs introduce additional layers of complexity to the hypoxic response. Based on novel interactions identified upstream and downstream of EGLNs, an integrated network connecting oxygen-sensing functions to metabolic and signaling pathways is gradually emerging with broad therapeutic implications.
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