Structure, expression and alternative splicing of the human c-ets-1 proto-oncogene

Abstract

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.