The genetics of jun.

Mutational analyses of Jun show that the leucine zipper mediates dimerization with other Jun molecules or with the Fos protein and determines the three-dimensional orientation of the adjacent basic region, facilitating interaction with DNA. The basic region of Jun is the DNA contact surface. Substitution of certain basic residues in this region leads to loss of DNA binding. Some basic region mutants also act as transdominant lethals: they are able to tie up wild type protein in inactive complexes. The definition of transactivator domains with deletion mutants of Jun appears to depend on the assay for transcriptional activation. CAT assays suggest multiple transactivator regions in the N-terminal third of Jun, while in vitro transcription assays detect a negative regulator of transcription in this region. Another transactivator domain appears to be located close to the basic region in both c-Jun and JunD. The genetics of Jun supports a hierarchical order of Jun functions in which dimerization is a prerequisite for both DNA binding and transcriptional activation, and DNA binding is needed for transcriptional activation.