O-GlcNAcylation links oncogenic signals and cancer epigenetics.
O-GlcNAcylation links oncogenic signals and cancer epigenetics.
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O-GlcNAc 酰化将致癌信号与癌症表观遗传学联系起来
DOI：
10.1007/s12672-021-00450-5
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发表时间：
2021-11-24
影响因子：
2.2
通讯作者：
Song T
中科院分区：
文献类型：
--
作者：
Sun L;Lv S;Song T
表观遗传修饰的普遍失调在癌症中起关键作用。靶向表观遗传异常是癌症治疗的新策略。了解传统的致癌因素如何引起表观遗传异常具有巨大的基本和翻译价值。 O-Glcnacylation是一种影响生理和病理生理学的蛋白质修饰。在哺乳动物中，O-Glcnacylation被一种单个酶OGT催化，并通过一种单个酶OGA去除。 O-Glcnacylation受供体UDP-GLCNAC的可用性影响，UDP-GLCNAC是由六胺生物发生途径（HBP）中的串行酶促反应产生的。 O-Glcnacylation调节了广泛的底物，包括许多参与表观遗传修饰的蛋白质。像表观遗传修饰一样，O-Glcnacylation的异常在癌症中也很常见。研究揭示了通过致癌信号对HBP酶和OGT/OGA的实质性影响。在这篇综述中，我们将首先总结致癌信号如何调节癌症中的HBP酶，OGT和OGA。然后，我们将将这些知识与最新的了解了解O-Glcnacylation如何调节表观遗传机制。因此，我们提出了一个信号轴，从致癌信号通过O-Glcnacylation失调到癌症的表观遗传异常。对该轴的进一步阐明不仅会提高我们对癌症生物学的理解，而且还可以为癌症治疗提供新的收入。
Prevalent dysregulation of epigenetic modifications plays a pivotal role in cancer. Targeting epigenetic abnormality is a new strategy for cancer therapy. Understanding how conventional oncogenic factors cause epigenetic abnormality is of great basic and translational value. O-GlcNAcylation is a protein modification which affects physiology and pathophysiology. In mammals, O-GlcNAcylation is catalyzed by one single enzyme OGT and removed by one single enzyme OGA. O-GlcNAcylation is affected by the availability of the donor, UDP-GlcNAc, generated by the serial enzymatic reactions in the hexoamine biogenesis pathway (HBP). O-GlcNAcylation regulates a wide spectrum of substrates including many proteins involved in epigenetic modification. Like epigenetic modifications, abnormality of O-GlcNAcylation is also common in cancer. Studies have revealed substantial impact on HBP enzymes and OGT/OGA by oncogenic signals. In this review, we will first summarize how oncogenic signals regulate HBP enzymes, OGT and OGA in cancer. We will then integrate this knowledge with the up to date understanding how O-GlcNAcylation regulates epigenetic machinery. With this, we propose a signal axis from oncogenic signals through O-GlcNAcylation dysregulation to epigenetic abnormality in cancer. Further elucidation of this axis will not only advance our understanding of cancer biology but also provide new revenues towards cancer therapy.
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DOI：
10.1074/jbc.m114.605881
发表时间：
2015-02-20
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bauer C;Göbel K;Nagaraj N;Colantuoni C;Wang M;Müller U;Kremmer E;Rottach A;Leonhardt H
通讯作者：
Leonhardt H
DOI：
10.1073/pnas.1912074117
发表时间：
2020-06-23
影响因子：
11.1
作者：
Boulard, Mathieu;Rucli, Sofia;Bestor, Timothy H.
通讯作者：
Bestor, Timothy H.
影响因子：
4.8
作者：
Chang, Q;Su, KH;Kudlow, JE
通讯作者：
Kudlow, JE
影响因子：
5.2
作者：
Bruce JIE;James AD
通讯作者：
James AD
影响因子：
7.7
作者：
Bauer, UM;Daujat, S;Kouzarides, T
通讯作者：
Kouzarides, T