TRANSFORMATION BY FOS PROTEINS REQUIRES A C-TERMINAL TRANSACTIVATION DOMAIN

The Fos family of proteins now includes seven members: the retroviral proteins FBR-v-Fos and FBJ-v-Fos and the cellular proteins c-Fos, FosB , FosB2, Fra1, and Fra2. Four proteins (FBR-v-Fos, FBJ-v-Fos, c-Fos, a nd FosB) transform established rodent fibroblast cell lines, while thr ee (FosB2, Fra1, and Fra2) do not. As all family members display seque nce-specific DNA-binding activity as part of a heterodimeric complex w ith Jun proteins, other features must account for the differences in t ransforming potential. We demonstrate here that all transforming membe rs have a C-terminal transactivation domain that is lacking in nontran sforming members. The nontransforming proteins Fra1 and Fra2 can be co nverted to transforming proteins by fusion of a transactivation domain from either FosB or VP16. We also demonstrate that differences in the basic region-leucine zipper domain affecting either the affinity or s equence specificity of DNA binding are not determinants of the differe nce in transforming potential among members of the Fos family. The res ults further define the functional requirements for transformation by Fos proteins and suggest that the subunit composition of AP1 complexes is an important determinant of mitogenic signalling capability.