The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors, codes for an RNA binding protein with novel regulatory domains.
The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors, codes for an RNA binding protein with novel regulatory domains.
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发表时间：
1994-10
期刊：
影响因子：
8
通讯作者：
T. Ohno;M. Ouchida;Leo M. Lee;Z. Gatalica;V. Rao;E. Reddy
中科院分区：
文献类型：
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作者：
T. Ohno;M. Ouchida;Leo M. Lee;Z. Gatalica;V. Rao;E. Reddy
EWS基因定位于人类22号染色体q12带，与多种人类实体瘤有关，包括尤文肉瘤、相关原始神经外胚层肿瘤、软组织恶性黑色素瘤和促结缔组织增生性小圆细胞肿瘤。在这些肿瘤中，EWS与编码转录激活因子/抑制因子的基因融合，如Fli-1或erg或ATF 1或wt 1。为了更好地了解EWS蛋白的功能，我们克隆了EWS cDNA。该cDNA的序列分析揭示了涉及两个外显子编码72个氨基酸的差异剪接。两种选择性剪接的转录物EWS和EWS-b在多种细胞中表达。由于EWS蛋白含有推定的保守RNA结合基序，我们研究了EWS蛋白的RNA结合特性。EWS-b蛋白在体外与RNA结合，特别是与聚G和聚U结合。RNA结合活性定位于羧基端86个氨基酸，它们构成RGG盒。因此，参与染色体易位的EWS的氨基末端结构域（NTD-EWS）可能调节EWS的RNA结合活性的特异性。在尤文氏肉瘤细胞中发现的EWS-erg嵌合蛋白作为转录激活因子发挥作用。EWS-erg嵌合蛋白的突变分析表明，NTD-EWS功能作为一个调控结构域的EWS-erg嵌合蛋白的转录激活特性。
The EWS gene, which maps to band q12 of human chromosome 22, is involved in a wide variety of human solid tumors including Ewing sarcoma, related primitive neuroectodermal tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors. In these tumors, the EWS is fused to genes encoding transcriptional activators/repressors, like Fli-1 or erg or ATF 1 or wt1. To better understand the function of the EWS protein, we cloned the EWS cDNA. Sequence analysis of this cDNA revealed differential splicing involving two exons encoding 72 amino acids. Both alternatively spliced transcripts, EWS and EWS-b, are expressed in a variety of cells. Because EWS proteins contain putative conserved RNA binding motifs, we studied the RNA binding properties of the EWS protein. The EWS-b protein binds to RNA in vitro and, specifically, to poly G and poly U. The RNA binding activity was localized to the carboxy terminal 86 amino acids, which constitute RGG box. Thus the amino terminal domain of EWS (NTD-EWS), which is involved in chromosome translocation may regulate the specificity of RNA binding activity of EWS. An EWS-erg chimeric protein, which is found in Ewing's sarcoma cells, functions as a transcriptional activator. Mutational analysis of EWS-erg chimeric protein revealed that NTD-EWS functions as a regulatory domain for the transcriptional activation properties of EWS-erg chimeric protein.