O-GlcNAc as an Integrator of Signaling Pathways.

O-GlcNAc as an Integrator of Signaling Pathways.
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DOI:
10.3389/fendo.2018.00599
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发表时间:
2018
影响因子:
5.2
通讯作者:
Yang X
Yang X
中科院分区:
医学2区
文献类型:
--
作者:
Ong Q;Han W;Yang X

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O-GlcNAc酰化是一种重要的翻译后修饰,由单对酶-O-GlcNAc转移酶(OGT)和O-GlcNAc酶(OGA)控制。这两种酶以营养和应激响应的方式介导多种细胞溶质、核和线粒体蛋白上的O-GlcNAc化的动态循环。虽然O-GlcNAc酰化的细胞功能已经出现,但关于酶对如何感知环境线索以引起分子和生理变化的精确机制知之甚少。在这篇综述中,我们讨论了如何OGT/OGA对作为一个代谢传感器,整合信号通路,考虑到他们的能力,从不同的合作伙伴接收信号输入,针对多个基板的时空特异性和易位到细胞的不同部分。我们还讨论了如何对维持细胞内的稳态信号及其生理相关性。更好地理解OGT/OGA作用的机制将使我们能够获得将细胞O-GlcNAc水平重置在最佳范围内的治疗益处。
O-GlcNAcylation is an important posttranslational modification governed by a single pair of enzymes–O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). These two enzymes mediate the dynamic cycling of O-GlcNAcylation on a wide variety of cytosolic, nuclear and mitochondrial proteins in a nutrient- and stress-responsive fashion. While cellular functions of O-GlcNAcylation have been emerging, little is known regarding the precise mechanisms how the enzyme pair senses the environmental cues to elicit molecular and physiological changes. In this review, we discuss how the OGT/OGA pair acts as a metabolic sensor that integrates signaling pathways, given their capability of receiving signaling inputs from various partners, targeting multiple substrates with spatiotemporal specificity and translocating to different parts of the cell. We also discuss how the pair maintains homeostatic signaling within the cell and its physiological relevance. A better understanding of the mechanisms of OGT/OGA action would enable us to derive therapeutic benefits of resetting cellular O-GlcNAc levels within an optimal range.
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