EFFICIENT INDUCTION OF FIBROSARCOMAS BY V-JUN REQUIRES MUTATIONS IN THE DNA-BINDING REGION AND THE TRANSACTIVATION DOMAIN

v-jun is the transforming gene of ASV 17, a retrovirus isolated from a spontaneous chicken fibrosarcoma. There are three mutations in the vi ral Jun protein (v-Jun) as compared to its cellular progenitor c-Jun: a deletion in the transactivation domain (called delta) and two amino acid substitutions in and near the DNA binding region. The effect of e ach of these mutations on fibrosarcoma development is described. All t hree mutations contribute towards tumor formation, and their cumulativ e effect makes v-Jun more tumorigenic compared to Jun proteins that ca rry only one or two of the mutations. Viruses rescued from tumors indu ced by c-Jun carrying the two amino acid substitutions in the DNA bind ing region have increased transforming and tumorigenic potential. Thes e increases are probably due to further mutations that result in the e xpression of a rearranged Jun protein. Taken together the results show that the evolution of the c-Jun oncoprotein to an efficient carcinoge n requires mutations in the transactivation and DNA binding regions.