EWS is a substrate of type I protein arginine methyltransferase, PRMT8.
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.
Kim
Jun-Dal
JD
Graduate School of Life & Environmental Science, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
Kako
Koichiro
K
Kakiuchi
Misako
M
Park
Gwi Gun
GG
Fukamizu
Akiyoshi
A
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
D008565:Membrane Proteins; D034802:RNA-Binding Protein EWS; D001120:Arginine; C505447:PRMT8 protein, human; D011484:Protein-Arginine N-Methyltransferases