A new group of conserved coactivators that increase the specificity of AP-1 transcription factors

Abstract

The Jun proteins are nuclear proteins that combine with Fos proteins to form a gene-regulatory protein, AP-1. They have highly conserved DNA-binding and dimerization domains, resulting in almost identical sequence-recognition properties. Nevertheless, there are many indications that each Jun protein activates a distinct and only partially overlapping set of AP-1 target genes. Using the more variable activation domain of c-Jun as a bait, we identified a protein, JAB1, that interacts with c-Jun and JunD, but not with JunB or v-Jun. As a result, JAB1 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 amino-terminal half of JAB1 is very similar to the amino terminal region of Pad1 from fission yeast, which was identified genetically as a coactivator of a subset of AP-1 target genes. JAB1 and Pad1 are also functionally interchangeable. They define a new group of coactivators that increase the specificity of target gene activation by AP-1 proteins.

Cross-family interaction between the bHLHZip USF and bZip Fra1 proteins results in down-regulation of AP1 activity

“…A direct e ect of USF on Jun homodimers also seems unlikely, since several results (this paper and data not shown) failed to detect any interaction between the two proteins. One possible explanation could be that USF interferes with a ternary factor such as CBP or the recently reported JAB1 factor (Arias et al, 1994;Claret et al, 1996), resulting in the observed drop of Jun activity. Additional experiments are required to further investigate this hypothesis.…”

Two bZIP proteins from Antirrhinum flowers preferentially bind a hybrid C‐box/G‐box motif and help to define a new sub‐family of bZIP transcription factors

“…In this respect, it is interesting that the related gene encoding OBF1 is most highly expressed in young meristematic regions of leaves (Singh et al, 1990). Transcriptional activation probably requires interaction with other factors, one possibility being the proteins binding to the neighbouring octomer motif conserved in many histone promoters, another being heterodimerization with other members of the bZIP protein family and yet another being binding to co-activators to increase bZIP activation specificity (Claret et al, 1996). The pattern of bZIP910 and bZIP911 gene expression shows a reasonably good correlation to expression of the gene encoding histone H4 in Antirrhinum inflorescences (Forbert et al, 1994) although post-transcriptional regulation may further modify the amount of each transcription factor active in any one cell.…”

Jab1 is overexpressed in human breast cancer and is a downstream target for HER-2/neu

“…1 Subsequent studies found that Jab1 is also the fifth component of the COP9/signalosome complex. 2,3 Recently, a new biological function of Jab1 has been suggested.…”