Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Dr. Aiguader 88, 08003 Barcelona, Spain.
Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain.
Int J Mol Sci. 2020 Feb 17;21(4):1351. doi: 10.3390/ijms21041351.
Protein arginine deimination leading to the non-coded amino acid citrulline remains a key question in the field of post-translational modifications ever since its discovery by Rogers and Simmonds in 1958. Citrullination is catalyzed by a family of enzymes called peptidyl arginine deiminases (PADIs). Initially, increased citrullination was associated with autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, as well as other neurological disorders and multiple types of cancer. During the last decade, research efforts have focused on how citrullination contributes to disease pathogenesis by modulating epigenetic events, pluripotency, immunity and transcriptional regulation. However, our knowledge regarding the functional implications of citrullination remains quite limited, so we still do not completely understand its role in physiological and pathological conditions. Here, we review the recently discovered functions of -mediated citrullination of the C-terminal domain of RNA polymerase II in transcriptional regulation in breast cancer cells and the proposed mechanisms to reshape the transcription regulatory network that promotes cancer progression.
自 1958 年 Rogers 和 Simmonds 发现以来，蛋白质精氨酸脱亚胺化导致非编码氨基酸瓜氨酸的问题一直是翻译后修饰领域的一个关键问题。瓜氨酸化是由一组称为肽基精氨酸脱亚氨酶 (PADIs) 的酶催化的。最初，瓜氨酸化的增加与自身免疫性疾病有关，包括类风湿性关节炎和多发性硬化症，以及其他神经紊乱和多种癌症。在过去的十年中，研究工作的重点是瓜氨酸化如何通过调节表观遗传事件、多能性、免疫和转录调控来促进疾病发病机制。然而，我们对瓜氨酸化的功能意义的了解仍然相当有限，因此我们仍然不完全了解它在生理和病理条件下的作用。在这里，我们综述了最近发现的 RNA 聚合酶 II C 末端结构域中 -介导的瓜氨酸化在乳腺癌细胞中转录调控中的作用，以及重塑促进癌症进展的转录调控网络的拟议机制。
