EWS is a substrate of type I protein arginine methyltransferase, PRMT8

Abstract

Abstract. EWS, a pro-oncoprotein which is encoded by the Ewing sarcoma (EWS) gene, contains arginine-glycine-glycine repeats (RGG box) in its COOH-terminus. We previously found that the RGG box of EWS is a target for dimethylation catalyzed by protein arginine methyltransferases (PRMTs). Although it has been observed that arginine residues in EWS are dimethylated in vivo, the endogenous enzyme(s) responsible for this reaction have not been identified to date. In the present study, we determined that EWS was physically associated with PRMT8, the novel eighth member of the PRMT family, through the COOH-terminal region of EWS including RGG3 with the NH 2 -terminal region of PRMT8 encompassing the S-adenosyl-L-methionine binding domain, and that arginine residues in EWS were asymmetrically dimethylated by PRMT8 using amino acid analysis with thinlayer chromatography. These results suggested that EWS is a substrate for PRMT8, as efficient as for PRMT1.

Ewing sarcoma EWS protein regulates midzone formation by recruiting Aurora B kinase to the midzone

“…Interestingly, the RGG domain of EWS was reported to be a substrate for methylation catalyzed by protein arginine methyltransferases (PRMT). [41][42][43][44] It is possible that the interaction between the EWS and Aurora B is regulated by the post transcriptional modification. The EWS R565A mutant is a powerful tool in determining how EWS participates in Aurora B-dependent midzone formation.…”

The protein arginine methyltransferase family: an update about function, new perspectives and the physiological role in humans

“…PRMT8 belongs to the type-I enzymes of methytransferases such as PRMT1, PRMT3, PRMT4, and PRMT6. Because of the close sequence homology of PRMT8 with PRMT1, both proteins have some overlapping substrates such as histones, RNA-binding proteins (e.g., hnRNPs) or the EWS protein responsible for causing Ewing sarcoma family tumor [108,109]. Over 20 proteins able to bind to PRMT8 were identified which contain putative methylation motifs and could be potential substrates for the enzyme, such as the cytoplasmic phosphoprotein caprin which plays a significant role in cell proliferation [109].…”

Transmethylation in immunity and autoimmunity

“…Arginine methylation occurs in a wide variety of substrates, including histones, transcription factors, cytoskeletal proteins, cytoplasmic signaling proteins, and apoptosis proteins (reviewed in [14] and [15]). Additional substrates of PRMT methylation have recently been identified and include the estrogen receptor ERα [16], splicing and elongation factors SAP49, UIC, and CA150 [17], FGF-2 [18], and Ewing Sarcoma Oncoprotein [19,20]. Further work is needed to define the sub-cellular distribution, potential redundancy, and expression profiles of these enzymes in specific cell types, particularly immunocytes.…”