TRANSFORMATION OF PRIMARY CHICK-EMBRYO FIBROBLASTS BY VIRALLY-EXPRESSED C-JUN REQUIRES NO MUTATION IN THE PROTEIN WHEN A SUFFICIENT LEVEL OF C-JUN PROTEIN IS REACHED

Proto-oncogene c-jun transforms primary chick embryo fibroblasts as a single gene when expressed from the replication competent retrovirus R (or RCAS). We have investigated whether transformation is caused by a ccumulating mutations within the proto-oncogene sequence during the re trotranscription process. c-jun coding sequences carried by three inde pendently isolated R-cJUN viruses have been cloned and entirely sequen ced. Two of these-were shown to carry no mutation demonstrating that d eregulated expression of a normal c-Jun product is sufficient for tran sformation. On the contrary when expressed from non replicative Rneo v ector lacking gag and pol sequences, the avian c-jun no longer transfo rmed. This difference is correlated with weaker c-Jun accumulation in the second case. When expressed from the same Rneo vector, low level o f v-Jun or of the heterologous mouse c-Jun still transform. Taken toge ther, these data strongly suggest that a threshold level of c-Jun prod uct is required for transformation and that this critical level can be lowered by mutations in c-jun or by the synthesis of an heterologous protein.