O-GlcNAcylation and O-GlcNAc Cycling Regulate Gene Transcription: Emerging Roles in Cancer.
O-GlcNAcylation and O-GlcNAc Cycling Regulate Gene Transcription: Emerging Roles in Cancer.
复制标题
O-Glcnacylation和O-GlCNAC循环调节基因转录：在癌症中的新作用。
DOI：
10.3390/cancers13071666
复制
发表时间：
2021-04-01
期刊：
影响因子：
5.2
通讯作者：
Slawson C
中科院分区：
文献类型：
--
作者：
Parker MP;Peterson KR;Slawson C
O-连接的β-N-乙酰葡萄糖胺（O-GlcNAc）是一种翻译后修饰（PTM），其通过己糖胺生物合成途径（HBP）将营养流与基因转录联系起来。越来越多的实验和临床数据表明，异常的O-GlcNAc化在癌症的发展和进展中起作用。在此，我们讨论了如何改变O-GlcNAc调节的转录机制，导致非典型基因表达的癌症。我们讨论了与研究O-GlcNAc功能相关的挑战，并提出了几种研究O-GlcNAc调控转录的新方法。O-连接的β-N-乙酰葡萄糖胺（O-GlcNAc）是细胞内蛋白质的单糖翻译后修饰（PTM），通过己糖胺生物合成途径（HBP）将营养素通量与基因组中顺式调控元件的控制联系起来。异常的O-GlcNAc化与癌症中基因表达的发展、进展和改变相关。O-GlcNAc循环被定义为通过O-GlcNAc转移酶（OGT）和O-GlcNAc酶（OGA）添加和随后去除修饰，为细胞调节基因表达的各个方面（包括RNA聚合酶功能、表观遗传动力学和转录因子活性）提供了新的方法。我们将重点关注磷酸化和O-GlcNAc化之间的复杂关系，通过OGT，OGA和激酶的同步作用，在RNA聚合酶II（RNAP II）前起始复合物的调节和RNAP II的羧基末端结构域的调节。此外，我们还讨论了TATA盒结合蛋白（TBP）的O-GlcNAc化如何改变细胞代谢。接下来，我们将以非详尽的方式讨论当前关于O-GlcNAc化如何通过转录因子或染色质重塑复合物功能的变化来驱动癌症中的基因转录的文献。最后，我们讨论了与研究O-GlcNAc酰基化相关的挑战，并提出了几种新的方法来研究O-GlcNAc调控的转录，这将促进我们对O-GlcNAc在癌症中的作用的理解。
O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification (PTM) linking nutrient flux through the hexosamine biosynthetic pathway (HBP) to gene transcription. Mounting experimental and clinical data implicates aberrant O-GlcNAcylation in the development and progression of cancer. Herein, we discuss how alteration of O-GlcNAc-regulated transcriptional mechanisms leads to atypical gene expression in cancer. We discuss the challenges associated with studying O-GlcNAc function and present several new approaches for studies of O-GlcNAc-regulated transcription. O-linked β-N-acetylglucosamine (O-GlcNAc) is a single sugar post-translational modification (PTM) of intracellular proteins linking nutrient flux through the Hexosamine Biosynthetic Pathway (HBP) to the control of cis-regulatory elements in the genome. Aberrant O-GlcNAcylation is associated with the development, progression, and alterations in gene expression in cancer. O-GlcNAc cycling is defined as the addition and subsequent removal of the modification by O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA) provides a novel method for cells to regulate various aspects of gene expression, including RNA polymerase function, epigenetic dynamics, and transcription factor activity. We will focus on the complex relationship between phosphorylation and O-GlcNAcylation in the regulation of the RNA Polymerase II (RNAP II) pre-initiation complex and the regulation of the carboxyl-terminal domain of RNAP II via the synchronous actions of OGT, OGA, and kinases. Additionally, we discuss how O-GlcNAcylation of TATA-box binding protein (TBP) alters cellular metabolism. Next, in a non-exhaustive manner, we will discuss the current literature on how O-GlcNAcylation drives gene transcription in cancer through changes in transcription factor or chromatin remodeling complex functions. We conclude with a discussion of the challenges associated with studying O-GlcNAcylation and present several new approaches for studying O-GlcNAc regulated transcription that will advance our understanding of the role of O-GlcNAc in cancer.
登录
查看更多内容
影响因子：
4.8
作者：
Banerjee, Sulagna;Sangwan, Veena;Saluja, Ashok K.
通讯作者：
Saluja, Ashok K.
影响因子：
4.8
作者：
Akan, Ilhan;Love, Dona C.;Hanover, John A.
通讯作者：
Hanover, John A.
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
影响因子：
4.3
作者：
Constable, Sandii;Lim, Jae-Min;Wells, Lance
通讯作者：
Wells, Lance
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