A ROLE FOR GROUCHO TETRAMERIZATION IN TRANSCRIPTIONAL REPRESSION

The Drosophila Groucho (Gro) protein is a corepressor required by a nu mber of DNA-binding transcriptional repressors. Comparison of Gro with its homologues in other eukaryotic organisms reveals that Gro contain s, in addition to a conserved C-terminal WD repeat domain, a conserved N-terminal domain, which has previously been implicated in transcript ional repression. We determined, via a variety of hydrodynamic measure ments as well as protein cross-linking, that native Gro is a tetramer in solution and that tetramerization is mediated by two putative amphi pathic alpha-helices (termed leucine zipper-like motifs) found in the N-terminal region, Point mutations in the leucine zipper-like motifs t hat block tetramerization also block repression by Gro, as assayed in cultured Drosophila cells with Gal4-Gro fusion proteins, Furthermore, the heterologous tetramerization domain from p53 fully substitutes for the Gro tetramerization domain in transcriptional repression. These f indings suggest that oligomerization is essential for Gro-mediated rep ression and that the primary function of the conserved N-terminal doma in is to mediate this oligomerization.