title: Transcriptional down-regulation through nuclear exclusion of EWS methylated by PRMT1.
abstract: The EWS gene is known to be chromosomally translocated and fused to various members of the DNA-binding transcription factors in Ewing's sarcoma and primitive neuroectodermal tumor. The product of this gene encodes the N-terminal transcriptional activation domain and the C-terminal RNA-binding domain containing an RNA-recognition motif and three arginine-glycine-glycine rich (RGG) motifs. Recently, we demonstrated EWS as a coactivator for hepatocyte nuclear factor 4 (HNF4)-mediated transcription. However, regulatory factors controlling EWS function are poorly characterized. In this study, we found that a protein arginine methyltransferase, PRMT1, physically interacts with EWS, whose cellular localization depends upon its RGG motifs targeted for methylation. Overexpression of PRMT1 down-regulates coactivator activity of EWS for HNF4-mediated transcription, because of the cytoplasmic retention of EWS from the nucleus. These results suggest that PRMT1 plays a post-translationally important role in regulating the transcriptional activity.
authors.affiliation: Center for Tsukuba Advanced Research Alliance, Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki 305-8577, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Araya
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hiraga
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kako
authors.forename: Yukitomo
authors.initials: Y
authors.lastname: Arao
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
mesh_terms: D001120:Arginine / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008745:Methylation; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D034802:RNA-Binding Protein EWS / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D034802:RNA-Binding Protein EWS; D012097:Repressor Proteins; D001120:Arginine; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases