TUMOR-INDUCTION BY V-JUN HOMODIMERS IN CHICKENS

To study the contribution of v-Jun homodimers to oncogenesis, me const ructed artificial v-Jun derivatives in which the natural dimerization domain of v-Jun was replaced by an heterologous homodimerization domai n from either the viral EB1 or the yeast GCN4 transcription factor. Th e resulting v-Jun chimeric proteins, called v-Jun(eb1) and v-Jun(gcn4) , which can no longer dimerize with Jun or Fos, should only form homod imers in the cell. Helper-independent retroviruses expressing v-Jun, v -Jun(eb1) and v-Jun(gcn4) were generated. AU three viruses transformed primary cultures of chick embryo cells with the same high efficiency and promoted local tumor growth after subcutaneous injection of infect ed cells in young animals. In contrast, after intravenous injection of viral suspensions into chick embryos, only the chimeric proteins prod uced internal tumors that were lethal. These tumors were leiomyosarcom as located within the liver and along the digestive tract. Thus, in vi vo, v-Jun(eb1) and v-Jun(gcn4) are more potent oncoproteins than v-Jun . These data demonstrate that when forced to accumulate, v-Jun homodim ers can induce tumors efficiently. They also show that the oncogenic p otential of v-Jun can be regulated through the properties of its dimer ization domain.