Molecular and Cellular Biology, December 1998, p. 7259-7268, Vol. 18, No. 12
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1569
Received 8 July 1998/Returned for modification 17 August 1998/Accepted 4 September 1998
The Drosophila Groucho (Gro) protein is a corepressor
required by a number of DNA-binding transcriptional repressors.
Comparison of Gro with its homologues in other eukaryotic organisms
reveals that Gro contains, in addition to a conserved C-terminal WD
repeat domain, a conserved N-terminal domain, which has previously been implicated in transcriptional repression. We determined, via a variety
of hydrodynamic measurements as well as protein cross-linking, that
native Gro is a tetramer in solution and that tetramerization is
mediated by two putative amphipathic
-helices (termed leucine zipper-like motifs) found in the N-terminal region. Point mutations in
the leucine zipper-like motifs that 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 findings
suggest that oligomerization is essential for Gro-mediated repression
and that the primary function of the conserved N-terminal domain is to mediate this oligomerization.
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