Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Base Sequence
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Basic Helix-Loop-Helix Transcription Factors
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Biomarkers, Tumor
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CCAAT-Enhancer-Binding Proteins*
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Cell Line
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Chloramphenicol O-Acetyltransferase / biosynthesis
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Chromosome Aberrations*
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Chromosome Disorders*
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / metabolism*
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Gene Expression*
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Helix-Loop-Helix Motifs
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Heterogeneous-Nuclear Ribonucleoproteins
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Humans
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Leukemia / genetics*
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Leukemia-Lymphoma, Adult T-Cell / genetics
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Leukemia-Lymphoma, Adult T-Cell / metabolism
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Liposarcoma / genetics
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Liposarcoma / metabolism
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Mice
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / metabolism*
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / metabolism*
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Proto-Oncogene Proteins*
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RNA-Binding Protein FUS
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Ribonucleoproteins / biosynthesis
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Ribonucleoproteins / metabolism*
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T-Cell Acute Lymphocytic Leukemia Protein 1
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Transcription Factor CHOP
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Transcription Factors / metabolism
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Transcription, Genetic*
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Transfection
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Translocation, Genetic
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Biomarkers, Tumor
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CCAAT-Enhancer-Binding Proteins
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DDIT3 protein, human
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DNA-Binding Proteins
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Ddit3 protein, mouse
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Heterogeneous-Nuclear Ribonucleoproteins
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Neoplasm Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins
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RNA-Binding Protein FUS
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Ribonucleoproteins
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T-Cell Acute Lymphocytic Leukemia Protein 1
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Tal1 protein, mouse
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Transcription Factors
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TAL1 protein, human
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Transcription Factor CHOP
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Chloramphenicol O-Acetyltransferase