Maf and Nrl can bind to AP-1 sites and form heterodimers with Fos and Jun.

The c-maf proto-oncogene and the neural retina specific gene nrl encode members of a new bZIP protein subfamily. We have examined the dimerization and DNA binding properties of this new protein family using polypeptides encompassing the leucine zipper and basic regions. Purified polypeptides bound specifically to the AP-1 and CRE sites as well as to variants of the AP-1 site. Maf and Nrl were also able to form heterodimers with Fos and Jun in vitro. All pairwise combinations of Maf, Nrl, Fos and Jun could be co-immunoprecipitated by antisera directed against either subunit. Heterodimers among these proteins bound to the AP-1 site, although with different affinities. Mutations in the leucine zipper dimerization interface or in the basic DNA contact region inhibited heterodimer formation and binding to the AP-1 site. These results indicate that Maf and Nrl together with Fos and Jun family proteins form a bZIP protein superfamily whose members can form an array of heterodimers that have overlapping DNA binding specificities.