CHIMERIC C-JUN CONTAINING AN HETEROLOGOUS HOMODIMERIZATION DOMAIN TRANSFORMS PRIMARY CHICK-EMBRYO FIBROBLASTS

To investigate a possible role for c-Jun homodimers in c-Jun-mediated transformation, we designed two chimeric c-Jun derivatives, called c-J un(eb1) and c-Jun(gcn4). In these chimeric derivatives the natural dim erization domain of c-Jun was replaced by the heterologous homodimeriz ation domain of the Epstein-Barr virus EB1 or the yeast GCN4 transcrip tion factor. Chick embryo fibroblasts chronically infected with retrov iruses expressing c-Jun, c-Jun(eb1) or c-Jun(gcn4) are transformed. In fection with each construction results in sustained growth in low seru m and development of colonies from single cells in agar with similar e fficiencies. In contrast to c-Jun, c-Jun(eb1) and c-Jun(gcn4) confer a dditional phenotypic alterations related to in vitro transformation in cluding a condensed cell morphology and ability to develop highly inva sive, fast growing colonies in agar. These data suggest that c-Jun hom odimers can transform chick embryo fibroblasts and activate cellular f unctions which influence cell morphology and invasive potential in aga r. These findings are consistent with the notion that cellular transfo rmation by c-jun is mediated by c-Jun homodimers.