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Protein arginine methyltransferases (PRMTs) as therapeutic targets

机译：蛋白质精氨酸甲基转移酶（PRMT）作为治疗靶标

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Introduction: Protein arginine methyltransferases (PRMTs) add one or two monomethyl groups to the guanidino nitrogen atoms of arginine residues, resulting in epigenetic modification of histones or changes of protein-protein interactions, which in turn leads to the regulation of a variety of biological functions, including transcriptional activation/repression, signal transduction, cell differentiation, and embryonic development. As dysregulation of PRMTs has been observed in diverse types of cancers and modulation of their levels affects cancer cell growth, these enzymes are considered to be potential therapeutic targets. Areas covered: In this review, we examined recent advances in our understanding of the regulatory mechanisms of PRMT activity and the biological roles of PRMTs in embryonic stem cell, Wnt/β-catenin signaling, and cancer development. Expert opinion: The roles of PRMTs have been fairly well established, but further studies are required to determine how PRMTs are regulated by cellular signaling pathways in vivo. Since the usage of adult stem cells is under intense scrutiny by society, identification of the roles of PRMTs in adult stem cells is expected in the near future. Although small molecules specific to PRMTs with high potency in vitro have been identified, development of small molecules that can regulate the activity of PRMTs in vivo is urgently required for therapeutic purposes.
机译：简介：蛋白质精氨酸甲基转移酶（PRMT）将一个或两个单甲基基团添加到精氨酸残基的胍基氮原子上，导致组蛋白的表观遗传修饰或蛋白质-蛋白质相互作用的改变，进而导致对多种生物学功能的调节包括转录激活/抑制，信号转导，细胞分化和胚胎发育。由于已经在各种类型的癌症中观察到PRMT的失调，并且其水平的调节会影响癌细胞的生长，因此这些酶被认为是潜在的治疗靶标。涵盖的领域：在这篇综述中，我们研究了PRMT活性调节机制以及PRMT在胚胎干细胞，Wnt /β-catenin信号传导和癌症发展中的生物学作用的理解方面的最新进展。专家意见：PRMT的作用已经相当确定，但是需要进一步的研究来确定PRMT在体内如何通过细胞信号通路调节。由于成体干细胞的使用受到社会的严格审查，因此预计在不久的将来鉴定PRMT在成体干细胞中的作用。尽管已经鉴定出对PRMT具有高体外效价的小分子，但迫切需要开发可调节PRMT在体内活性的小分子以达到治疗目的。

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