Proto-oncogene FosB: the amino terminus encodes a regulatory function required for transformation

Overexpression of some members of the Fos gene family, including FosB, leads to transformation of established rodent fibroblasts. We have previously shown that transformation by FosB requires the presence of a C-terminal transcriptional activation domain. We now report that transformation by FosB also requires an intact DNA-binding domain composed of the functionally bipartite basic region and leucine zipper as well as sequences present in the N terminus that serve a regulatory function. Deletion of the N-terminal sequences results in proteins impaired in transcriptional activation and transformation. This region does not itself function as a transcriptional activation domain but instead regulates the transactivation functions present in the FosB-Jun complex. The requirement for this N-terminal region can be abolished by the presence of a strong constitutive activation domain. The primary sequence of the region that we have defined is highly conserved in the Fos family of proteins, suggesting functional conservation.