Structure, expression and alternative splicing of the human c-ets-1 proto-oncogene.
The avian acute leukemia virus E26 induces a mixed erythroid-myeloid leukemia in chicken and carries two distinct oncogenes, v-myb and v-ets. It was shown that there exist two ets loci in humans, c-ets-1 and c-ets-2, which were mapped to human chromosome 11 and 21, respectively. The human c-ets-1 proto-oncogene locus was shown to translocate from chromosome 11 to 9 or 4 in certain patients with acute monocytic leukemia. In order to understand the functional role of c-ets-1 proto-oncogene, we have made a cDNA library from MOLT-4 cells and isolated seven c-ets-1 positive cDNA clones. Analysis of two cDNA clones revealed a complete open reading frame of the c-ets-1 proto-oncogene. Except for 81 nucleotides at the 5'-end (downstream of initiation codon) and 39 nucleotides at the 3'-end (upstream of termination codon), the c-ets-1 cDNA is approximately 82% homologous to v-ets oncogene sequences and encodes a 441-residue protein (c-ets-1a) which contains contiguous 5' and 3' regions of the v-ets oncogene as in the case of chicken. Sequence analysis also revealed alternative splicing, giving rise to another related c-ets-1 polypeptide (c-ets-1b) lacking 87 amino acids. Our results suggest that differential RNA splicing allows the synthesis of at least two related c-ets-1 polypeptides from a single c-ets-1 proto-oncogene.
Reddy
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Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
Rao
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D000595:Amino Acid Sequence; D009189:Avian Myeloblastosis Virus / Q000235:genetics; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D011519:Proto-Oncogenes; D012326:RNA Splicing; D012191:Retroviridae Proteins / Q000235:genetics; D015682:Retroviridae Proteins, Oncogenic; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors; D014407:Tumor Cells, Cultured / Q000032:analysis
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012191:Retroviridae Proteins; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; C050379:oncogene proteins v-ets; D004247:DNA