Pbx1 is converted into a transcriptional activator upon acquiring the N-terminal region of E2A in pre-B-cell acute lymphoblastoid leukemia.
Pbx1 is converted into a transcriptional activator upon acquiring the N-terminal region of E2A in pre-B-cell acute lymphoblastoid leukemia.
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在前 B 细胞急性淋巴细胞白血病中，Pbx1 在获得 E2A N 末端区域后转化为转录激活因子。
DOI：
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发表时间：
1993
影响因子：
11.1
通讯作者：
Cornelis Murre
中科院分区：
文献类型：
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作者：
M. A. V. Duk;P. Voorhoeve;Cornelis Murre
25% 的儿童前 B 细胞急性淋巴细胞白血病 (ALL) 的特征是 t(1;19)(q23;p13.3) 染色体易位。该易位将 E2A 基因的 5' 区域连接到 Pbx1 基因的 3' 区域。该嵌合基因编码的蛋白质包含与 Pbx1 的 C 端区域融合的 E2A N 端转录激活结构域，其中包含假定的同源结构域。在这里，我们表明 Pbx1 同源域优先结合序列 ATCAATCAA。我们进一步表明，含有 Pbx1 结合位点的启动子被嵌合 E2A-Pbx1 蛋白激活，但不被 Pbx1 激活。这些结果表明 t(1;19) 易位将非激活 DNA 结合蛋白转化为有效的转录激活因子，这表明了一种不寻常的致癌转化机制。
Twenty-five percent of human pediatric pre-B-cell acute lymphoblastic leukemias (ALLs) are characterized by the t(1;19)(q23;p13.3) chromosomal translocation. This translocation joins the 5' region of the E2A gene to the 3' region of the Pbx1 gene. The protein encoded by this chimeric gene contains the N-terminal transcriptional activation domain of E2A fused to the C-terminal region of Pbx1, which contains a putative homeodomain. Here we show that the Pbx1 homeodomain preferentially binds the sequence ATCAATCAA. We further show that promoters containing Pbx1-binding sites are activated by the chimeric E2A-Pbx1 protein but not by Pbx1. These results indicate that the t(1;19) translocation converts a nonactivating DNA-binding protein into a potent transcriptional activator, suggesting an unusual mechanism for oncogenic transformation.