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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.

A Role for Groucho Tetramerization in Transcriptional Repression

Guoqing Chen, Pierre H. Nguyen, and Albert J. Courey*

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 alpha -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.

* Corresponding author. Mailing address: Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095-1569. Phone: (310) 825-2530. Fax: (310) 206-4038. E-mail: courey{at}chem.ucla.edu.

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.


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