Hangzhou Medical College, Hangzhou, Zhejiang, China.
Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.
Int J Cancer. 2021 Jan 15;148(2):267-276. doi: 10.1002/ijc.33205. Epub 2020 Aug 8.
Peptidylarginine deiminases (PADs) catalyze the conversion of arginine residues to citrulline residues on target proteins in the presence of calcium ions. This elaborate type of posttranslational modification is termed citrullination. PADs may regulate gene transcriptional activity via histone citrullination. There has been an increasing appreciation for the roles of PADs in a wide variety of biological processes. In this review article, we summarize recent evidence indicating that PADs and citrullinated proteins are involved in several physiological and pathological processes related to cancer. Of particular interest is that PAD2 and PAD4 exhibit characteristic expression levels, activities and specific biological effects in diverse types of cancer. We also list several PAD inhibitors, propose the possible mechanisms underlying the biological actions of PAD-mediated protein citrullination in experimental models and discuss the potential therapeutic value of PADs and their inhibitors for disease diagnosis and treatment.
肽基精氨酸脱亚氨酶（PADs）在钙离子存在的条件下，催化靶蛋白上精氨酸残基向瓜氨酸残基的转化。这种精细的翻译后修饰类型被称为瓜氨酸化。PADs 可以通过组蛋白瓜氨酸化来调节基因转录活性。人们越来越认识到 PADs 在多种生物学过程中的作用。在这篇综述文章中，我们总结了最近的证据，表明 PADs 和瓜氨酸化蛋白参与了与癌症相关的多种生理和病理过程。特别值得关注的是，PAD2 和 PAD4 在多种类型的癌症中表现出特征性的表达水平、活性和特定的生物学效应。我们还列出了几种 PAD 抑制剂，提出了 PAD 介导的蛋白质瓜氨酸化在实验模型中生物学作用的可能机制，并讨论了 PADs 及其抑制剂在疾病诊断和治疗方面的潜在治疗价值。
