Raposo Anita E, Piller Sabine C
School of Science and Health, Western Sydney University, Penrith, NSW 2751 Australia.
Cell Div. 2018 Mar 20;13:3. doi: 10.1186/s13008-018-0036-2. eCollection 2018.
Protein arginine methylation is a common post-translational modification where a methyl group is added onto arginine residues of a protein to alter detection by its binding partners or regulate its activity. It is known to be involved in many biological processes, such as regulation of signal transduction, transcription, facilitation of protein-protein interactions, RNA splicing and transport. The enzymes responsible for arginine methylation, protein arginine methyltransferases (PRMTs), have been shown to methylate or associate with important regulatory proteins of the cell cycle and DNA damage repair pathways, such as cyclin D1, p53, p21 and the retinoblastoma protein. Overexpression of PRMTs resulting in aberrant methylation patterns in cancers often correlates with poor recovery prognosis. This indicates that protein arginine methylation is also an important regulator of the cell cycle, and consequently a target for cancer regulation. The effect of protein arginine methylation on the cell cycle and how this emerging key player of cell cycle regulation may be used in therapeutic strategies for cancer are the focus of this review.
蛋白质精氨酸甲基化是一种常见的翻译后修饰,在该修饰过程中,一个甲基基团被添加到蛋白质的精氨酸残基上,从而改变其结合伴侣对其的识别或调节其活性。已知它参与许多生物学过程,如信号转导调控、转录、促进蛋白质-蛋白质相互作用、RNA剪接和转运。负责精氨酸甲基化的酶,即蛋白质精氨酸甲基转移酶(PRMTs),已被证明可使细胞周期和DNA损伤修复途径的重要调节蛋白甲基化或与其结合,如细胞周期蛋白D1、p53、p21和视网膜母细胞瘤蛋白。PRMTs的过表达导致癌症中出现异常甲基化模式,这通常与恢复预后不良相关。这表明蛋白质精氨酸甲基化也是细胞周期的重要调节因子,因此是癌症调控的一个靶点。蛋白质精氨酸甲基化对细胞周期的影响以及这个新兴的细胞周期调控关键因子如何用于癌症治疗策略是本综述的重点。