A Human Raf-responsive Zinc-finger Protein That Binds to Divergent Sequences

LZ321, a human liver cDNA, encodes a protein that bound to a Drosophila tramtrack binding site, GGTCCT. The sequence of LZ321 matched that of RREB1, a transcription factor that bound to a Ras responsive element (RRE) very different from the sequence with which we isolated LZ321. We therefore examined the binding of RREB1/LZ321 to different ligands. It bound to the GGTCCT-containing ligand and to the RRE with similar affinities (Kd50-60 nM), but did not bind to a consensus RREB1 binding site. The RREB1/LZ321 protein contains four C2H2zinc-fingers, the C-terminal two of which retained specific DNA binding to both ligands. A trimer of the GGTCCT site functioned as an enhancer in both CV-1 and H4IIE-C3 cells. Thus RREB1/LZ321 could function as a downstream activator in the Ras-Raf signaling pathway through different cis -acting elements. A longer human protein, Finb, contains RREB1/LZ321, and there are close homologs in both chicken and Drosophila, arguing that it plays important roles. The ability of transcription factors such as RREB1/LZ321 to bind diverse sequences gives them the potential to regulate previously unsuspected genes.