Laboratory of Molecular Immunology, Rega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Laboratory of Molecular Immunology, Rega Institute for Medical Research, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Trends Cell Biol. 2022 Sep;32(9):746-761. doi: 10.1016/j.tcb.2022.01.014. Epub 2022 Feb 21.
Peptidylarginine deiminases (PADs) are calcium-dependent enzymes that mediate citrullination, an irreversible post-translational modification (PTM). PAD enzymes have received increasing attention in (patho-)physiology since multi-omics analysis accelerated their expression profiling. Here, we provide a comprehensive overview of PAD expression at the RNA and protein levels, and a list of annotated substrates per PAD isozyme. We discuss novel roles of citrullination in cellular growth, epigenetic regulation, tissue remodeling, inflammation, and cancer in mouse models and humans. Additionally, we cluster similar effects of protein deimination to offer a different perspective and improve our understanding of citrullination in health and disease. Citrullination should no longer be considered as a rare PTM, but as an important regulatory mechanism in physiology and pathology.
肽基精氨酸脱亚氨酶（PADs）是一种依赖于钙的酶，可介导瓜氨酸化，这是一种不可逆的翻译后修饰（PTM）。多组学分析加速了其表达谱的研究，因此 PAD 酶在（病理）生理学中受到越来越多的关注。在这里，我们全面概述了 PAD 在 RNA 和蛋白质水平上的表达，并列出了每种 PAD 同工酶的注释底物列表。我们讨论了瓜氨酸化在细胞生长、表观遗传调控、组织重塑、炎症和癌症中的新作用，这些作用在小鼠模型和人类中均有体现。此外，我们还对蛋白脱亚氨基作用进行聚类，以提供不同的视角，从而加深对瓜氨酸化在健康和疾病中的作用的理解。瓜氨酸化不应再被视为一种罕见的 PTM，而应被视为生理和病理过程中的一种重要调节机制。
