PRMT5在癌症中的研究进展

蛋白质精氨酸甲基转移酶(protein arginine methyltransferases,PRMTs)是真核生物中常见的一种酶,可催化组蛋白和非组蛋白底物中的精氨酸残基发生甲基化。在人类的基因组中,PRMTs由9个基因编码。作为最主要的II型精氨酸甲基转移酶,PRMT5是PRMT家族成员之一,参与了包括信号转导、转录调控、RNA剪切及DNA损伤修复在内的多种生物学过程;在多种人类恶性肿瘤中表达上调,发挥着类似致癌基因的作用。该文对PRMT5在多种癌症中的研究进展进行综述,并对现有的PRMT5小分子抑制剂进行总结(包括其结构和潜在的癌症靶向治疗应用前景)。

Recent Advances of PRMT5 in Cancer

Protein arginine methylation is one of the most abundant and evolutionarily conserved post-translational modifications catalyzed by the PRMTs(protein arginine methyltransferases).PRMTs,encoded by nine genes in the human genome,can methylate histone and nonhistone proteins.As the main type II arginine methyltransferase,PRMT5 has been implicated in the control of many cellular processes such as cell cycle progression,signal transduction,gene expression regulation,RNA splicing and DNA-damage response.Overexpression of PRMT5 is frequently found in numerous human cancers with evidence indicative of an oncogene-like function.Here,an update on the recent advances of PRMT5 in cancer research is provided and the promise of targeting PRMT5 by small molecular inhibitors is discussed for treating aggressive human cancers.