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Structure and biological activity of human homologs of the raf/mil oncogene
Abstract:
Two human genes homologous to the raf/mil oncogene have been cloned and sequenced. One, c-raf-2, is a processed pseudogene; the other, c-raf-1, contains nine exons homologous to both raf and mil and two additional exons homologous to mil. A 3' portion of c-raf-1 containing six of the seven amino acid differences relative to murine v-raf can substitute for the 3' portion of v-raf in a transformation assay. Sequence homologies between c-raf-1 and Moloney leukemia virus at both ends of v-raf indicate that the viral gene was acquired by homologous recombination. Although the data are consistent with the traditional model of retroviral transduction, they also raise the possibility that the transduction occurred in a double crossover event between proviral DNA and the murine gene.
Insights
Researchers cloned and sequenced human raf/mil oncogene homologs. The c-raf-1 gene, containing unique exons, showed functional similarity to viral raf genes, suggesting a novel viral gene acquisition mechanism.
Area of Science:
- Molecular Biology
- Oncogenesis
- Genetics
Background:
- The raf/mil oncogene family plays a critical role in cellular signaling pathways.
- Understanding the origins and structure of oncogenes is crucial for cancer research.
Purpose of the Study:
- To clone and sequence human genes homologous to the raf/mil oncogene.
- To investigate the structural and functional relationship between human c-raf-1 and viral v-raf genes.
- To elucidate the mechanism of viral oncogene acquisition.
Main Methods:
- Gene cloning and sequencing.
- Functional assays involving gene substitution.
- Sequence homology analysis.
Main Results:
- Two human homologs were identified: c-raf-2 (a pseudogene) and c-raf-1.
- c-raf-1 possesses unique exons and shares significant homology with both raf and mil.
- A specific domain of c-raf-1 could functionally replace the corresponding v-raf domain in a transformation assay.
- Sequence analysis suggests homologous recombination between c-raf-1 and Moloney leukemia virus.
Conclusions:
- The human c-raf-1 gene is a functional homolog of the viral raf/mil oncogene.
- The findings support a model of viral gene acquisition via homologous recombination.
- A double crossover event is proposed as a potential mechanism for viral oncogene transduction.