Chimeric c-Jun containing an heterologous homodimerization domain transforms primary chick embryo fibroblasts

Abstract

To investigate a possible role for c-Jun homodimers in c-Jun-mediated transformation, we designed two chimeric c-Jun derivatives, called c-Juneb1 and c-Jungcn4. In these chimeric derivatives the natural dimerization domain of c-Jun was replaced by the heterologous homodimerization domain of the Epstein-Barr virus EB1 or the yeast GCN4 transcription factor. Chick embryo fibroblasts chronically infected with retroviruses expressing c-Jun, c-Juneb1 or c-Jungcn4 are transformed. Infection with each construction results in sustained growth in low serum and development of colonies from single cells in agar with similar efficiencies. In contrast to c-Jun, c-Juneb1 and c-Jungcn4 confer additional phenotypic alterations related to in vitro transformation including a condensed cell morphology and ability to develop highly invasive, fast growing colonies in agar. These data suggest that c-Jun homodimers can transform chick embryo fibroblasts and activate cellular functions which influence cell morphology and invasive potential in agar. These findings are consistent with the notion that cellular transformation by c-jun is mediated by c-Jun homodimers.