TRANSCRIPTIONAL ACTIVATION BY TAL1 AND FUS-CHOP PROTEINS EXPRESSED IN ACUTE MALIGNANCIES AS A RESULT OF CHROMOSOMAL-ABNORMALITIES

被引:93
作者
SANCHEZGARCIA, I
RABBITTS, TH
机构
[1] Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 2QH, Hills Road
关键词
T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA; FUSION PROTEINS; DNA BINDING; SOLID TUMORS; ACTIVATION DOMAIN;
D O I
10.1073/pnas.91.17.7869
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 pro,ides 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.
引用
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页码:7869 / 7873
页数:5
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