Both Jun and Fos contribute to transcription activation by the heterodimer.

Comparison of the amino acid sequence of the three members of the mouse jun proto-oncogene family, c-jun, jun B and jun D, reveals several homologous segments. The most C-terminal of them including a leucine zipper motif and a cluster of basic amino acids was previously identified as the DNA binding domain. By deletion analysis, we show that three conserved domains in the N-terminal region are crucial for transactivation by Jun homodimers. Only one of these is predicted to form an acidic amphipathic alpha-helix. The addition of Fos and the formation of Jun-Fos heterodimers strongly increases the transactivation level. Jun mutants that are inactive alone gain partial or full activity in the presence of Fos. This increase strongly depends on the presence of the C-terminal domain of Fos. These results show that in Jun-Fos heterodimers both the N-terminal part of Jun and the C-terminal part of Fos contribute to transactivation with a more pronounced role for the latter.