Monté D, Baert J L, Defossez P A, de Launoit Y, Stéhelin D
Unité d'Oncologie Molèculaire, CNRS URA 1160, Institut Pasteur de Lille, France.
Oncogene. 1994 May;9(5):1397-406.
The ets-related transcription factors PEA3 and ER81 have recently been isolated and characterized in the mouse. They share 95% identity in a 85 amino acid (AA) domain termed the ETS domain which is responsible for DNA binding, and therefore they form an Ets family group. By screening a human testis cDNA library with a probe containing the mouse PEA3 ETS domain, we isolated a 2.2 kb clone containing a 510 AA open reading frame. Since the ETS domain, which is localized in the carboxy terminal region of the encoded protein, is 95% and 96% identical to that of PEA3 and ER81, respectively, we named this new member 'Ets Related Molecule PEA3-like' (ERM). Although the first 120 AA in the amino-terminal region of ERM share 47% identity with PEA3 and 66% with ER81, ERM contains a central region of approximately 35 AA not found in the two mouse proteins. Gel shift analysis indicates that the full-length ERM protein is able to bind specifically to an oligonucleotide containing the consensus nucleotide core sequence GGAA recognized by the Ets proteins. Moreover, in vitro translation of 83 AA of the ERM ETS domain led to the production of a truncated protein which also binds to DNA. Though differential expression is observed in primary tumors and normal lymphocytes do not express ERM, this gene is almost ubiquitously expressed in human normal tissues. ERM mRNA is highly expressed in brain as well as in placenta and, to a lesser degree, in lung, pancreas, and heart. Moreover, almost all human cell lines tested express it at varying levels. In mouse tissues, we showed that PEA3 and ER81 mRNAs display restricted expression, whereas ERM is almost ubiquitously expressed as observed for human tissues. Altogether these results indicate that ERM is clearly a new ets family member and not the human equivalent of PEA3 or ER81.
最近在小鼠中分离并鉴定了与ets相关的转录因子PEA3和ER81。它们在一个名为ETS结构域的85个氨基酸（AA）区域中具有95%的同一性，该结构域负责DNA结合，因此它们形成了一个Ets家族组。通过用含有小鼠PEA3 ETS结构域的探针筛选人睾丸cDNA文库，我们分离出一个2.2 kb的克隆，其中包含一个510 AA的开放阅读框。由于位于编码蛋白羧基末端区域的ETS结构域分别与PEA3和ER81的ETS结构域具有95%和96%的同一性，我们将这个新成员命名为“Ets相关分子PEA3样”（ERM）。尽管ERM氨基末端区域的前120个AA与PEA3具有47%的同一性，与ER81具有66%的同一性，但ERM包含一个约35个AA的中央区域，这在两种小鼠蛋白中未发现。凝胶迁移分析表明，全长ERM蛋白能够特异性结合含有Ets蛋白识别的共有核苷酸核心序列GGAA的寡核苷酸。此外，对ERM ETS结构域的83个AA进行体外翻译产生了一种截短蛋白，该蛋白也能与DNA结合。虽然在原发性肿瘤中观察到差异表达，正常淋巴细胞不表达ERM，但该基因在人正常组织中几乎普遍表达。ERM mRNA在脑中以及胎盘中高度表达，在肺、胰腺和心脏中表达程度较低。此外，几乎所有测试的人细胞系都以不同水平表达它。在小鼠组织中，我们表明PEA3和ER81 mRNA显示出受限表达，而ERM几乎如在人组织中观察到的那样普遍表达。总之，这些结果表明ERM显然是一个新的Ets家族成员，而不是PEA3或ER81的人类等同物。
