School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Pathogens. 2012 Sep 19;1(1):52-64. doi: 10.3390/pathogens1010052.
Although there is increasing evidence that aberrant expression of those enzymes which control protein arginine methylation contribute to carcinogenesis, their de-regulation by oncogenic viruses in primary cells has yet to be reported. We first show that the protein arginine methyltransferases, CARM1, PRMT1 and PRMT5 are strongly expressed in Hodgkin Reed-Sternberg (HRS) cells, and up-regulated in Hodgkin's lymphoma (HL) cell lines. Given that Epstein-Barr virus (EBV) can be detected in approximately 50% of primary HL, we next examined how EBV infection of germinal centre (GC) B cells, the presumptive precursors of HRS cells, modulated the expression of these proteins. EBV infection of GC B cells was followed by the up-regulation of CARM1, PRMT1 and PRMT5, and by the down-regulation of the arginine deiminase, PADI4. Latent membrane protein 1 (LMP1), the major EBV transforming gene was shown to induce PRMT1 in GC B cells and in a stably transfected B cell line. The recent development of compounds which inhibit PRMT-mediated reactions provides a compelling case for continuing to dissect the contribution of virus induced changes in these proteins to lymphomagenesis.
虽然越来越多的证据表明，控制蛋白质精氨酸甲基化的酶的异常表达有助于致癌作用，但它们在原代细胞中被致癌病毒的失调尚未被报道。我们首先表明，蛋白质精氨酸甲基转移酶 CARM1、PRMT1 和 PRMT5 在霍奇金氏 Reed-Sternberg (HRS) 细胞中强烈表达，并在霍奇金淋巴瘤 (HL) 细胞系中上调。鉴于大约 50%的原发性 HL 中可检测到 Epstein-Barr 病毒 (EBV)，我们接下来检查了 EBV 感染生发中心 (GC) B 细胞，即 HRS 细胞的假定前体，如何调节这些蛋白的表达。GC B 细胞感染 EBV 后，CARM1、PRMT1 和 PRMT5 的表达上调，而精氨酸脱亚氨酶 PADI4 的表达下调。潜伏膜蛋白 1 (LMP1)，主要的 EBV 转化基因，被证明在 GC B 细胞和稳定转染的 B 细胞系中诱导 PRMT1。最近开发的抑制 PRMT 介导反应的化合物为继续剖析这些蛋白的病毒诱导变化对淋巴瘤发生的贡献提供了强有力的理由。
