title: A human Raf-responsive zinc-finger protein that binds to divergent sequences.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202-5122, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: H J
authors.initials: HJ
authors.lastname: Edenberg
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics; D020218:Response Elements / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D016335:Zinc Fingers; D018631:ras Proteins / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C101743:RREB1 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; C075878:ttk protein, Drosophila; D004247:DNA; D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins