title: EWS is a substrate of type I protein arginine methyltransferase, PRMT8.
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 NH2-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 thin-layer chromatography. These results suggested that EWS is a substrate for PRMT8, as efficient as for PRMT1.
authors.affiliation: Graduate School of Life & Environmental Science, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Jun-Dal
authors.initials: JD
authors.lastname: Kim
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kako
authors.forename: Misako
authors.initials: M
authors.lastname: Kakiuchi
authors.forename: Gwi Gun
authors.initials: GG
authors.lastname: Park
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
mesh_terms: D001120:Arginine / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D002460:Cell Line; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008745:Methylation; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D034802:RNA-Binding Protein EWS / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D008565:Membrane Proteins; D034802:RNA-Binding Protein EWS; D001120:Arginine; C505447:PRMT8 protein, human; D011484:Protein-Arginine N-Methyltransferases