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

Proteins that appear to participate in transcriptional control of gene expression are increasingly implicated in leukemias and malignant sol id tumors. We report here that the N-terminal domains of the proteins TAL1 (ectopically activated in T-cell acute leukemias after chromosoma l abnormalities caused by V-D-J recombinase error) (V, variable; D, di versity; 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 report er genes. The result with TAL1 pro,ides evidence that transcriptional activation can be mediated by a gene activated by translocation in T-c ell acute leukemias. In the case of the liposarcoma, transactivation b y the FUS-CHOP protein occurs because the FUS transcriptional activati on domain is added to the DNA-binding CHOP protein normally lacking su ch 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.