Transcriptional down-regulation through nuclear exclusion of EWS methylated by PRMT1
Transcriptional down-regulation through nuclear exclusion of EWS methylated by PRMT1
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DOI：
10.1016/j.bbrc.2005.02.018
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发表时间：
2005-04-08
影响因子：
3.1
通讯作者：
Fukamizu, A
中科院分区：
文献类型：
--
作者：
Araya, N;Hiraga, H;Fukamizu, A
已知EWS基因在尤文氏肉瘤和原始神经外胚层肿瘤中染色体易位并融合到DNA结合转录因子的各种成员。该基因的产物编码N-末端转录激活结构域和C-末端RNA结合结构域，其含有RNA识别基序和三个富含甘氨酸-甘氨酸-甘氨酸（RGG）基序。最近，我们证明EWS作为肝细胞核因子4（HNF 4）介导的转录的共激活剂。然而，控制EWS功能的调节因素的特点很差。在这项研究中，我们发现，蛋白质精氨酸甲基转移酶，PRMT 1，物理相互作用与EWS，其细胞定位取决于其RGG基序靶向甲基化。PRMT 1的过表达下调了HNF 4介导的转录EWS的共激活因子活性，因为EWS从细胞核中保留在细胞质中。这些结果表明，PRMT 1在转录活性的调控中起着重要的后转录作用。(c)2005年爱思唯尔公司All rights reserved.
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. (c) 2005 Elsevier Inc. All rights reserved.