Tumor induction by v-Jun homodimers in chickens.
To study the contribution of v-Jun homodimers to oncogenesis, we constructed artificial v-Jun derivatives in which the natural dimerization domain of v-Jun was replaced by an heterologous homodimerization domain from either the viral EB1 or the yeast GCN4 transcription factor. The resulting v-Jun chimeric proteins, called v-Juneb1 and v-Jungcn4, which can no longer dimerize with Jun or Fos, should only form homodimers in the cell. Helper-independent retroviruses expressing v-Jun, v-Juneb1 and v-Jungcn4 were generated. All three viruses transformed primary cultures of chick embryo cells with the same high efficiency and promoted local tumor growth after subcutaneous injection of infected cells in young animals. In contrast, after intravenous injection of viral suspensions into chick embryos, only the chimeric proteins produced internal tumors that were lethal. These tumors were leiomyosarcomas located within the liver and along the digestive tract. Thus, in vivo, v-Juneb1 and v-Jungcn4 are more potent oncoproteins than v-Jun. These data demonstrate that when forced to accumulate, v-Jun homodimers can induce tumors efficiently. They also show that the oncogenic potential of v-Jun can be regulated through the properties of its dimerization domain.
D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000096:biosynthesis; D015870:Gene Expression; D016758:Genes, jun; D005822:Genetic Vectors; D005895:Gizzard, Avian / Q000473:pathology; D007150:Immunohistochemistry; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D016759:Oncogene Protein p65(gag-jun) / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D012190:Retroviridae; D029701:Saccharomyces cerevisiae Proteins; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000096:biosynthesis
D017931:DNA Primers; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D046911:Macromolecular Substances; D016759:Oncogene Protein p65(gag-jun); D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014764:Viral Proteins; D015500:Chloramphenicol O-Acetyltransferase; D011494:Protein Kinases