Localization and modulation of the DNA-binding activity of the human c-ets-1 protooncogene.
The avian acute leukemia virus (E26) induces a mixed erythroid-myeloid leukemia in chickens and carries two distinct oncogenes, v-myb and v-ets. The viral protein responsible for transformation is a gag-myb-ets fusion protein that is located in the nucleus of the transformed cells. The cellular homologue of v-ets (c-ets-1) is highly expressed in lymphoid cells and differs from the v-ets gene at its carboxy terminal region. Here, we show that both the c-ets-1 and v-ets gene products are DNA-binding proteins and their DNA-binding activity is located in the carboxy terminal (46 amino acid residues) region. It appears that this DNA-binding activity is modulated by the extreme carboxy terminal region. The amino acid sequences of the putative ets DNA-binding domain at its carboxy terminal region showed a helix-turn-helix secondary structure. Exchanging the nonhomologous extreme carboxy terminal regions of c-ets-1 with v-ets gene sequences showed differences in DNA-binding affinity, indicating that these differences may be partly responsible for the activation of the ets oncogene.
Reddy
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Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140.
Rao
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D000595:Amino Acid Sequence; D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics; D001665:Binding Sites; D002471:Cell Transformation, Neoplastic; D002846:Chromatography, Affinity; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D011519:Proto-Oncogenes; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D004247:DNA; D011505:Protein-Tyrosine Kinases