Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus.

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Abstract
A unique acutely transforming replication-defective mouse type C virus, 3611-murine sarcoma virus (3611-MSV), was molecularly cloned and its acquired oncogene was characterized. The viral genome closely resembles Moloney (M) murine leukemia virus (MuLV), except for a substitution in M-MuLV in the middle of p30 and the middle of the polymerase gene (pol). Heteroduplex analysis revealed that 2.4 kilobases of M-MuLV DNA were replaced by 1.2 kilobases of cellular DNA. The junctions between viral and cellular sequences were determined by DNA sequence analysis to be 517 nucleotides into the p30 sequence and 1920 nucleotides into the pol sequence. Comparison of the transforming gene from 3611-MSV, designated v-raf, with previously isolated retrovirus oncogenes either by direct hybridization or by comparison of restriction fragments of their cellular homologues shows it to be unique. Transfection of [mouse] NIH 3T3 cells with cloned 3611-MSV proviral DNA leads to highly efficient transformation and the recovered virus elicits tumors in mice typical of the 3611-MSV virus. Transfected NIH 3T3 cells express 2 3611-MSV-specific polyproteins (P75 and P90), both of which contain NH2-terminal gag gene-encoded components linked to the acquired sequence (v-raf) translational product. The cellular homologue, c-raf, is present in 1 or 2 copies per haploid genome in mouse and human DNA.