Research Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women's University, Seoul, 04310, Republic of Korea.
Natural Product Research Institute, Korea Institute of Science and Technology, Gangneung, 25451, Republic of Korea.
Exp Mol Med. 2021 May;53(5):788-808. doi: 10.1038/s12276-021-00613-y. Epub 2021 May 18.
Protein methylation, a post-translational modification (PTM), is observed in a wide variety of cell types from prokaryotes to eukaryotes. With recent and rapid advancements in epigenetic research, the importance of protein methylation has been highlighted. The methylation of histone proteins that contributes to the epigenetic histone code is not only dynamic but is also finely controlled by histone methyltransferases and demethylases, which are essential for the transcriptional regulation of genes. In addition, many nonhistone proteins are methylated, and these modifications govern a variety of cellular functions, including RNA processing, translation, signal transduction, DNA damage response, and the cell cycle. Recently, the importance of protein arginine methylation, especially in cell cycle regulation and DNA repair processes, has been noted. Since the dysregulation of protein arginine methylation is closely associated with cancer development, protein arginine methyltransferases (PRMTs) have garnered significant interest as novel targets for anticancer drug development. Indeed, several PRMT inhibitors are in phase 1/2 clinical trials. In this review, we discuss the biological functions of PRMTs in cancer and the current development status of PRMT inhibitors in cancer therapy.
蛋白质甲基化是一种翻译后修饰（PTM），存在于从原核生物到真核生物的各种细胞类型中。随着表观遗传学研究的迅速发展，蛋白质甲基化的重要性得到了强调。组蛋白蛋白的甲基化有助于表观遗传组蛋白密码，不仅是动态的，而且还受到组蛋白甲基转移酶和去甲基酶的精细调控，这些酶对于基因的转录调控至关重要。此外，许多非组蛋白蛋白也被甲基化，这些修饰调控着多种细胞功能，包括 RNA 加工、翻译、信号转导、DNA 损伤反应和细胞周期。最近，人们注意到蛋白质精氨酸甲基化的重要性，特别是在细胞周期调控和 DNA 修复过程中。由于蛋白质精氨酸甲基化的失调与癌症的发展密切相关，因此精氨酸甲基转移酶（PRMTs）作为新型抗癌药物开发的靶点引起了广泛关注。事实上，已有几种 PRMT 抑制剂进入 1/2 期临床试验。在这篇综述中，我们讨论了 PRMTs 在癌症中的生物学功能以及 PRMT 抑制剂在癌症治疗中的最新发展状况。
