Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S5B6, Canada.
Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S5B6, Canada.
Brain Res. 2019 Mar 15;1707:164-171. doi: 10.1016/j.brainres.2018.11.024. Epub 2018 Nov 19.
Lysine methylation is well-documented and relatively well-understood with respect to histone modification and the epigenetic regulation of gene expression. Enzymes called lysine methyltransferases (KMTs) are capable of methylating lysine residues on histone tails, while the opposing lysine demethylases (KDMs) are capable of removing the methyl groups. This balance of dynamic methylation of histone proteins effectively alters gene expression, and has been widely studied with many applications in neurological disease. While histone methylation is an extensive field of research, lysine methylation has received considerable attention in recent years, following the discovery of a handful of non-histone substrates for KMTs. With the expanding repertoire of non-histone substrates, exploration into the cellular functions regulated by this dynamic post-translational modification has become an intriguing research question. Recent studies have implicated non-histone methylation in many crucial cell processes, such as signal transduction, apoptosis, and proliferation. Although most of the current research in this emerging field is streamlined for applications in cancer, it seems that lysine methylation of non-histone proteins could also be relevant in neurodegenerative disease. This review will summarize what is known about the role of histone lysine methylation in neurodegenerative diseases, and explore the links between recently identified non-histone methylated proteins, and the brain. Our goal is to connect the emerging field of non-histone protein methylation with neurodegenerative research.
赖氨酸甲基化在组蛋白修饰和基因表达的表观遗传调控方面已有充分的记载和相对较好的理解。称为赖氨酸甲基转移酶（KMTs）的酶能够在组蛋白尾部的赖氨酸残基上进行甲基化，而相反的赖氨酸去甲基酶（KDMs）能够去除甲基。组蛋白蛋白的这种动态甲基化平衡有效地改变了基因表达，并在神经疾病的许多应用中得到了广泛的研究。虽然组蛋白甲基化是一个广泛的研究领域，但赖氨酸甲基化在近年来受到了相当多的关注，这是在发现了少数 KMT 的非组蛋白底物之后。随着非组蛋白底物的不断扩展，探索这种动态翻译后修饰所调控的细胞功能已成为一个有趣的研究问题。最近的研究表明，非组蛋白甲基化参与了许多关键的细胞过程，如信号转导、细胞凋亡和增殖。尽管该新兴领域的大多数当前研究都针对癌症的应用进行了简化，但似乎非组蛋白的赖氨酸甲基化也可能与神经退行性疾病有关。本综述将总结组蛋白赖氨酸甲基化在神经退行性疾病中的作用，并探讨最近鉴定的非组蛋白甲基化蛋白与大脑之间的联系。我们的目标是将非组蛋白蛋白甲基化的新兴领域与神经退行性研究联系起来。
