Parker Matthew P, Peterson Kenneth R, Slawson Chad
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Cancers (Basel). 2021 Apr 1;13(7):1666. doi: 10.3390/cancers13071666.
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.
O-连接的β-N-乙酰葡糖胺（O-GlcNAc）是细胞内蛋白质的一种单糖翻译后修饰（PTM），它通过己糖胺生物合成途径（HBP）将营养物质通量与基因组中顺式调控元件的控制联系起来。异常的O-GlcNAcylation与癌症的发生、发展以及基因表达的改变有关。O-GlcNAc循环被定义为通过O-GlcNAc转移酶（OGT）添加修饰以及随后由O-GlcNAcase（OGA）去除修饰，这为细胞调节基因表达的各个方面提供了一种新方法，包括RNA聚合酶功能、表观遗传动力学和转录因子活性。我们将重点关注RNA聚合酶II（RNAP II）预起始复合物调控中磷酸化与O-GlcNAcylation之间的复杂关系，以及通过OGT、OGA和激酶的同步作用对RNAP II羧基末端结构域的调控。此外，我们还将讨论TATA框结合蛋白（TBP）的O-GlcNAcylation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-GlcNAcylation如何通过转录因子或染色质重塑复合物功能的变化在癌症中驱动基因转录的文献。最后，我们将讨论研究O-GlcNAcylation所面临的挑战，并提出几种研究O-GlcNAc调控转录的新方法，这些方法将增进我们对O-GlcNAc在癌症中作用的理解。
