Transcriptional activation by TAL1 and FUS-CHOP proteins expressed in acute 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 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.
Sánchez-García
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Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.
Rabbitts
T H
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D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D015870:Gene Expression; D018257:Helix-Loop-Helix Motifs; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism; D008080:Liposarcoma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins / Q000096:biosynthesis / Q000378:metabolism*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014178:Translocation, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D022762:CCAAT-Enhancer-Binding Proteins; D015500:Chloramphenicol O-Acetyltransferase; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D051742:Transcription Factor CHOP; D014157:Transcription Factors; C497249:DDIT3 protein, human; C497250:Ddit3 protein, mouse; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human