Lattouf Hanine, Poulard Coralie, Le Romancer Muriel
INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Oncotarget. 2019 May 7;10(34):3151-3153. doi: 10.18632/oncotarget.26883.
Protein arginine methyltransferases (PRMTs) catalyze the methylation of arginine residues on both histones and non-histone proteins. PRMT5, a member of the PRMT family, is overexpressed in a wide variety of cancers and its activity is associated with cell transformation. Moreover, its expression is associated with a decrease in patient survival in several cancers, a rationale for developing highly potent inhibitors of its enzymatic activity. However, most studies do not take into account the subcellular localization of PRMT5, which can modify its properties. Indeed, our team recently showed that PRMT5 nuclear expression is associated with prolonged survival. These results corroborated findings in prostate cancer, in which the nuclear fraction of PRMT5 was responsible for inhibiting cell growth, while the cytoplasmic fraction promoted cell growth. In conclusion, this criterion should be evaluated prior to administering PRMT5 inhibitors, which may have adverse effects.
蛋白质精氨酸甲基转移酶(PRMTs)催化组蛋白和非组蛋白上精氨酸残基的甲基化。PRMT家族成员之一PRMT5在多种癌症中过表达,其活性与细胞转化相关。此外,在几种癌症中,其表达与患者生存率降低有关,这是开发其酶活性强效抑制剂的一个理由。然而,大多数研究没有考虑PRMT5的亚细胞定位,而亚细胞定位会改变其特性。事实上,我们的团队最近表明,PRMT5的核表达与生存期延长相关。这些结果证实了前列腺癌中的研究发现,其中PRMT5的核部分负责抑制细胞生长,而细胞质部分促进细胞生长。总之,在使用可能有不良反应的PRMT5抑制剂之前,应评估这一标准。