Efficient induction of fibrosarcomas by v-jun requires mutations in the DNA binding region and the transactivation domain.

ABSTRACT

v-jun is the transforming gene of ASV 17, a retrovirus isolated from a spontaneous chicken fibrosarcoma. There are three mutations in the viral 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 each of these mutations on fibrosarcoma development is described. All three mutations contribute towards tumor formation, and their cumulative effect makes v-Jun more tumorigenic compared to Jun proteins that carry only one or two of the mutations. Viruses rescued from tumors induced by c-Jun carrying the two amino acid substitutions in the DNA binding region have increased transforming and tumorigenic potential. These increases are probably due to further mutations that result in the expression of a rearranged Jun protein. Taken together the results show that the evolution of the c-Jun oncoprotein to an efficient carcinogen requires mutations in the transactivation and DNA binding regions.