An autonomous N‐terminal transactivation domain in Fos protein plays a crucial role in transformation.

To date, three functional domains have been defined in c‐Fos and v‐Fos proteins and have been shown to play a role in transactivation: the leucine zipper mediating hetero‐dimerization, the basic DNA contact site, and a C‐terminally located transactivation domain (C‐TA) harbouring the HOB1 and HOB2 motifs. While the bZip region, consisting of the leucine zipper and the DNA contact site, is indispensable for transformation, the C‐TA domain is not required and is actually altered by internal deletions in the FBR‐MuSV. We now show that the N‐terminal regions of c‐Fos and v‐Fos contain a second transactivation domain (N‐TA). A functionally crucial motif within the N‐TA domain, termed NTM, was pinpointed to a approximately 25 amino acid stretch around positions 60‐84 which is highly conserved in FosB. Analysis of LexA fusion proteins showed that the N‐TA domains of both c‐Fos and FosB function in an autonomous fashion in both fibroblasts and yeast. Most importantly, deletion of the NTM motif impairs the transforming properties of v‐Fos. Apart from the bZip region, the N‐TA domain is the only functional domain required for transformation by v‐Fos, at least when its expression is driven by the strong FBR‐MuSV‐LTR promoter.