Nucleotide sequence of avian retroviral oncogene v-mil: homologue of murine retroviral oncogene v-raf

Abstract

Eukaryotic cells contain genes termed proto-oncogenes (c-onc) which have the potential to transform cells in culture and induce tumours in vivo. Most of these genes have been identified by their occasional incorporation into retroviral genomes which can act as natural transducing vectors for these and perhaps other cellular genes^1,2. Cell-derived oncogenes of retroviruses (v-onc) are associated mostly with the induction of mesenchymal tumours whereas carcinoma induction is rare³. One of these rare carcinoma-inducing viruses is the acutely transforming avian retrovirus MH2 (refs 3–5). Recently we^6,7 and others⁸ have shown that this virus carries a novel putative oncogene, v-mil, in addition to the known oncogene v-myc. While the transforming ability of v-mil has not been directly established, we have recently discovered by hybridization analysis that v-mil is homologous to v-raf (ref. 9), the transforming gene of the murine retrovirus 3611 MSV (ref. 10). Both viruses express the mil/raf oncogene product as a gag-fusion polyprotein^6,11, while the myc oncogene of MH2 is expressed via a subgenomic mRNA¹². Here we report the complete nucleotide sequence of v-mil and compare it with that of v-raf³⁴. The 80% homology between the nucleotide sequences and the 94% homology between the predicted amino acid sequences of the two viral genes clearly indicate that these are the avian and murine forms of the same gene. Comparison of the two sequences with that of the human cellular homologue¹³ (T. I. Bonner et al., manuscript in preparation) indicates that v-raf has more 3′ untranslated sequences while v-mil has additional sequences from two 5′ exons of the cellular homologue. Although the mil/raf amino acid sequences reveal partial homology to that of the v-src product, no tyrosine-specific protein kinase activity is detected for the gag–mil and the gag–raf hybrid proteins.