Posttranslational modifications (PTMs) such as protein arginine methylation are involved in the regulation of diverse cellular processes such as epigenetic modifications, DNA damage response (DDR), RNA processing, signal transduction, and immune responses. Protein methyltransferases (PRMTs), which mediate arginine methylation, have been studied because of their dysregulation in several diseases. PRMT5, a type II arginine methyltransferase is relevant to cancer progression. Inhibition/deletion of PRMT5 augments tumor immunity by modulating Tip60 histone acetyltransferase activity and FOXP3 levels and limits the inhibitory function of T regulatory (Treg) cells, providing an approach to treat human cancers in an effective and exclusive manner. The activity of PRMT5 is regulated at various levels involving interaction with regulatory proteins, PTM modifications and noncoding RNA. Several PRMT5 inhibitors have been developed and are undergoing clinical trials or are in the preclinical phases. The current review concerns the regulation, biological functions, and therapeutic approaches for targeting PRMT5 with a focus on its role in tumor immunity. Critically, PRMT5 regulates the expression of Tip60 which we have shown is needed for FOXP3 regulatory interactions with DNA.

中文翻译：

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PRMT5 和 Tip60 在肿瘤免疫中修改 FOXP3 功能

蛋白质精氨酸甲基化等翻译后修饰 (PTM) 参与多种细胞过程的调节，例如表观遗传修饰、DNA 损伤反应 (DDR)、RNA 加工、信号转导和免疫反应。已经研究了介导精氨酸甲基化的蛋白质甲基转移酶 (PRMT)，因为它们在多种疾病中失调。PRMT5 是一种 II 型精氨酸甲基转移酶，与癌症进展有关。PRMT5 的抑制/缺失通过调节 Tip60 组蛋白乙酰转移酶活性和 FOXP3 水平来增强肿瘤免疫力，并限制 T 调节 (Treg) 细胞的抑制功能，提供一种以有效和独特的方式治疗人类癌症的方法。PRMT5 的活性在涉及与调节蛋白相互作用的各个水平上受到调节，PTM 修饰和非编码 RNA。已经开发了几种 PRMT5 抑制剂并正在进行临床试验或处于临床前阶段。目前的综述关注靶向 PRMT5 的调控、生物学功能和治疗方法，重点是其在肿瘤免疫中的作用。至关重要的是，PRMT5 调节 Tip60 的表达，我们已经证明这是 FOXP3 与 DNA 调节相互作用所必需的。