Van Dijk M A, Voorhoeve P M, Murre C
Department of Biology 0116, University of California, San Diego, La Jolla 92093.
Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6061-5. doi: 10.1073/pnas.90.13.6061.
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.
25%的人类小儿前B细胞急性淋巴细胞白血病（ALL）具有t(1;19)(q23;p13.3)染色体易位特征。这种易位将E2A基因的5'区域与Pbx1基因的3'区域连接起来。由该嵌合基因编码的蛋白质包含与Pbx1的C末端区域融合的E2A的N末端转录激活结构域，Pbx1的C末端区域包含一个假定的同源结构域。我们在此表明，Pbx1同源结构域优先结合序列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)易位将一种非激活的DNA结合蛋白转化为一种强效转录激活因子，提示了一种致癌转化的异常机制。
