title: Arginine Methyltransferases Are Regulated by Epstein-Barr Virus in B Cells and Are Differentially Expressed in Hodgkin's Lymphoma.
abstract: 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.
authors.affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. s.m.leonard@bham.ac.uk.
authors.forename: Sarah
authors.initials: S
authors.lastname: Leonard
authors.affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. n.gordon@bham.ac.uk.
authors.forename: Naheema
authors.initials: N
authors.lastname: Gordon
authors.affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. smithny@adf.bham.ac.uk.
authors.forename: Nikki
authors.initials: N
authors.lastname: Smith
authors.affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. rowem@adf.bham.ac.uk.
authors.forename: Martin
authors.initials: M
authors.lastname: Rowe
authors.affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. murraypg@adf.bham.ac.uk.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Murray
authors.affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK. c.b.woodman@bham.ac.uk.
authors.forename: Ciarán B
authors.initials: CB
authors.lastname: Woodman