PRMT5与JAKs/STATs通路的相互作用及其机制的研究进展

Research Progress of Interaction between PRMT5 and JAKs/STATs Signaling Pathway

蛋白精氨酸甲基转移酶5(PRMT5)属于Ⅱ型甲基转移酶,主要催化组蛋白和非组蛋白物质的精氨酸残基的对称二甲基化修饰。PRMT5通过表观遗传学调控靶基因的表达或信号分子的翻译后修饰,从而参与多种细胞进程。PRMT5可能是一种癌基因,并且通过多种肿瘤抑制基因或者信号分子的修饰导致肿瘤的发生。骨髓增殖性肿瘤(MPN)中普遍存在JAK2基因的突变并且导致Janus激酶(JAKs)/信号转导和转录激活因子(STATs)信号通路的激活,JAKs/STATs在MPN的发病机制中起着重要的作用,而且有证据表明PRMT5在MPN发展中有重要作用。

The protein arginine methytransferase 5 （PRMT5） is a type II methytransferase that symmetrically methyl- ates arginine residues of histone and nonhistone substrates, thereby regulating a variety of cellular process through epigenetic control of target gene expression or pose-translational modification. Mechanistic studies have suggested that PRMT5 may function as an oncogene to drive cancer cell growth by epigenetic repression of several tumor suppressor genes or by post- translational modification of signaling molecules. The prevalence of activating JAK2 mutations in myeloproliferative neoplasms （MPN） suggests that aberrant gene expression due to deregulated signaling of the JAKs/STATs pathway plays an important role in the etiology of these diseases. Moreover, there is evidence that PRMT5 plays an important role in MPN development.