Sánchez-García I, Rabbitts T H
Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7869-73. doi: 10.1073/pnas.91.17.7869.
Proteins that appear to participate in transcriptional control of gene expression are increasingly implicated in leukemias and malignant solid tumors. We report here that the N-terminal domains of the proteins TAL1 (ectopically activated in T-cell acute leukemias after chromosomal abnormalities caused by V-D-J recombinase error) (V, variable; D, diversity; J, joining) and FUS-CHOP (a liposarcoma tumor-specific fusion protein that is produced as a result of a chromosomal translocation) can function as transcription activators of specific responsive reporter genes. The result with TAL1 provides evidence that transcriptional activation can be mediated by a gene activated by translocation in T-cell acute leukemias. In the case of the liposarcoma, transactivation by the FUS-CHOP protein occurs because the FUS transcriptional activation domain is added to the DNA-binding CHOP protein normally lacking such activity. Therefore, the association of transcriptional activation and DNA-binding elements is a common consequence in proteins activated or newly created as fusion proteins after chromosomal translocations in acute leukemias and in malignant solid tumors.
那些似乎参与基因表达转录调控的蛋白质，越来越多地与白血病和恶性实体瘤相关联。我们在此报告，蛋白质TAL1（在V-D-J重组酶错误导致染色体异常后，在T细胞急性白血病中异位激活）（V，可变区；D，多样区；J，连接区）和FUS-CHOP（一种脂肪肉瘤肿瘤特异性融合蛋白，由染色体易位产生）的N端结构域可作为特定反应性报告基因的转录激活因子。TAL1的结果表明，转录激活可由T细胞急性白血病中因易位而激活的基因介导。就脂肪肉瘤而言，FUS-CHOP蛋白的反式激活发生是因为FUS转录激活结构域添加到了通常缺乏这种活性的DNA结合蛋白CHOP上。因此，转录激活与DNA结合元件的关联是急性白血病和恶性实体瘤染色体易位后作为融合蛋白被激活或新产生的蛋白质中的常见现象。
