A human Raf-responsive zinc-finger protein that binds to divergent sequences

Lu Zhang, Jinghua Zhao, Howard J. Edenberg

Research output: Contribution to journalArticle

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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 (K(d) 50-60 nM), but did not bind to a consensus RREB1 binding site. The RREB1/LZ321 protein contains four C2H2 zinc-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.

Original languageEnglish (US)
Pages (from-to)2947-2956
Number of pages10
JournalNucleic acids research
Volume27
Issue number14
DOIs
StatePublished - Jul 15 1999

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ASJC Scopus subject areas

  • Genetics

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