Lee Young-Ho, Stallcup Michael R
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Los Angeles, California 90089-9176, USA.
Mol Endocrinol. 2009 Apr;23(4):425-33. doi: 10.1210/me.2008-0380. Epub 2009 Jan 22.
Endocrine regulation frequently culminates in altered transcription of specific genes. The signal transduction pathways, which transmit the endocrine signal from cell surface to the transcription machinery, often involve posttranslational modifications of proteins. Although phosphorylation has been by far the most widely studied protein modification, recent studies have indicated important roles for other types of modification, including protein arginine methylation. Ten different protein arginine methyltransferase (PRMT) family members have been identified in mammalian cells, and numerous substrates are being identified for these PRMTs. Whereas major attention has been focused on the methylation of histones and its role in chromatin remodeling and transcriptional regulation, there are many nonhistone substrates methylated by PRMTs. This review primarily focuses on recent progress on the roles of the nonhistone protein methylation in transcription. Protein methylation of coactivators, transcription factors, and signal transducers, among other proteins, plays important roles in transcriptional regulation. Protein methylation may affect protein-protein interaction, protein-DNA or protein-RNA interaction, protein stability, subcellular localization, or enzymatic activity. Thus, protein arginine methylation is critical for regulation of transcription and potentially for various physiological/pathological processes.
内分泌调节常常最终导致特定基因转录的改变。将内分泌信号从细胞表面传递至转录机制的信号转导途径，通常涉及蛋白质的翻译后修饰。尽管磷酸化是迄今为止研究最为广泛的蛋白质修饰，但最近的研究表明其他类型的修饰也具有重要作用，包括蛋白质精氨酸甲基化。在哺乳动物细胞中已鉴定出10种不同的蛋白质精氨酸甲基转移酶（PRMT）家族成员，并且正在为这些PRMT鉴定大量底物。尽管主要注意力集中在组蛋白甲基化及其在染色质重塑和转录调控中的作用，但也存在许多被PRMT甲基化的非组蛋白底物。本综述主要关注非组蛋白蛋白质甲基化在转录中作用的最新进展。共激活因子、转录因子和信号转导子等蛋白质的甲基化在转录调控中发挥重要作用。蛋白质甲基化可能影响蛋白质 - 蛋白质相互作用、蛋白质 - DNA或蛋白质 - RNA相互作用、蛋白质稳定性、亚细胞定位或酶活性。因此，蛋白质精氨酸甲基化对于转录调控以及潜在的各种生理/病理过程至关重要。
