A NEW GROUP OF CONSERVED COACTIVATORS THAT INCREASE THE SPECIFICITY OF AP-1 TRANSCRIPTION FACTORS

THE Jun proteins are nuclear proteins that combine with Fos proteins t o form a gene-regulatory protein, AP-1. They have highly conserved DNA -binding and dimerization domains, resulting in almost identical seque nce-recognition properties(1-3). Nevertheless, there are many indicati ons that each Jun protein activates a distinct and only partially over lapping set of AP-1 target genes(4-6). Using the more variable activat ion domain of c-Jun as a bait, we identified a protein, JAB1, that int eracts with c-Jun and JunD, but not with JunB or v-Jun. As a result, J AB1 selectively potentiates transactivation by only c-Jun or JunD, In vitro, JAB1 specifically stabilizes complexes of c-Jun or JunD with AP -1 sites and does not affect binding of either JunB or v-Jun. The amin o-terminal half of JAB1 is very similar to the amino terminal region o f Pad1 from fission yeast, which was identified genetically as a coact ivator of a subset of AP-1 target genes(7). JAB1 and Pad1 are also fun ctionally interchangeable. They define a new group of coactivators tha t increase the specificity of target gene activation by AP-1 proteins.