瓜氨酸化(citrullination)是指在蛋白质精氨酸脱亚胺酶(peptidylarginine deiminases,PADs)作用下蛋白质肽链中的精氨酸残基转化为瓜氨酸残基的过程,是一种重要的蛋白质翻译后修饰的过程。目前,已有5种PAD酶在人体组织中被发现,分别为PAD1-4和PAD6,PAD2和PAD4在许多恶性肿瘤组织中呈高表达。研究发现组蛋白、细胞角蛋白、纤维粘连蛋白、白介素8等蛋白质均可被瓜氨酸化,并与肿瘤细胞的增殖、分化、凋亡、迁移等密切相关。本文从表观遗传学观点出发就PADs介导的蛋白质瓜氨酸化与肿瘤关系的研究进展进行综述,为深入探讨肿瘤的发生发展机制及其治疗提供新的研究思路。
Protein citrullination referred to the process that peptidylarginine deiminase(PAD) catalyses arginine residual to citruline one. It was one of the most important post-translational modifications of proteins. Currently five mammalian PAD family members had been discovered, in which PAD2 and PAD4 were demonstrated to be overexpressed in many types of malignant tumors. It had been demonstrated that histone, cytokeratin, fibronectin and interleukin 8, et al could be citrullinated, and were closely correlated with the proliferation, differentiation, apoptosis, invasion and metastasis of tumors. In view of epigenetic perspectives, the progress on the relationship between PAD-mediated Citrullination and malignant tumors would be summarized in this review.