Dysregulation of protein argininemethyltransferase in the pathogenesis of cancerpy

Abstract

Arginine methylation is considered to be one of the most permanent and one of the most frequent post-translational modifications. The reaction of transferring a methyl group from S-adenosylmethionine to arginine residue is catalyzed by aginine methyltransferase (PRMT). In humans there are nine members of the PRMT family, named in order of discovery of PRMT1- PRMT9. Arginine methyltransferases were divided into three classes: I, II, III, with regard to the product of the catalyzed reaction. The products of their activity are, respectively, the following: asymmetric dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA) and monomethylarginine (MMA). These modifications significantly affect the chromatin functions; therefore, they can act as co-activators or suppressors of the transcription process. Arginine methylation plays a crucial role in many biological processes in a human organism. Among others, it participates in signal transduction control, mRNA splicing and the regulation of basic cellular processes such as proliferation, differentiation, migration and apoptosis. There is increasing evidence that dysregulation of PRMT levels may lead to the cancer transformation of cells. The correlation between increased PRMT level and cancer has been demonstrated in the following: breast, ovary, lung and colorectal cancer. The activity of arginine methyltransferase can be regulated by small molecule PRMT inhibitors. To date, three substances that inhibit PRMT activity have been evaluated in clinical trials and exhibit anti-tumor activity against hematological cancer. It is believed that the use of specific PRMT inhibitors may become a new, effective and safe treatment of oncological diseases.