Previous Article | Next Article 
Molecular and Cellular Biology, May 2004, p. 4341-4350, Vol. 24, No. 10
0270-7306/04/$08.00+0 DOI: 10.1128/MCB.24.10.4341-4350.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Groucho Oligomerization Is Required for Repression In Vivo
Haiyun Song,1 Peleg Hasson,2 Zeev Paroush,2 and Albert J. Courey1*
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095-1569,1
Department of Biochemistry, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel2
Received 19 October 2003/
Returned for modification 22 December 2003/
Accepted 11 February 2004
Drosophila Groucho (Gro) is a member of a family of metazoan corepressors with widespread roles in development. Previous studies indicated that a conserved domain in Gro, termed the Q domain, was required for repression in cultured cells and mediated homotetramerization. Evidence presented here suggests that the Q domain contains two coiled-coil motifs required for oligomerization and repression in vivo. Mutagenesis of the putative hydrophobic faces of these motifs, but not of the hydrophilic faces, prevents the formation of both tetramers and higher order oligomers. Mutagenesis of the hydrophobic faces of both coiled-coil motifs in the context of a Gal4-Gro fusion protein prevents repression of a Gal4-responsive reporter in S2 cells, while mutagenesis of a single motif weakens repression. The finding that the repression directed by the single mutants depends on endogenous wild-type Gro further supports the idea that oligomerization plays a role in repression. Overexpression in the fly of forms of Gro able to oligomerize, but not of a form of Gro unable to oligomerize, results in developmental defects and ectopic repression of Gro target genes in the wing disk. Although the function of several corepressors is suspected to involve oligomerization, these studies represent one of the first direct links between corepressor oligomerization and repression in vivo.
* Corresponding author. Mailing address: Department of Chemistry and Biochemistry, UCLA, 607 Charles E. Young Drive, East, Box 951569, Los Angeles, CA 90095-1569. Phone: (310) 825-2530. Fax: (310) 206-4038. E-mail: courey{at}chem.ucla.edu.
Molecular and Cellular Biology, May 2004, p. 4341-4350, Vol. 24, No. 10
0022-538X/04/$08.00+0 DOI: 10.1128/MCB.24.10.4341-4350.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Choi, H.-K., Choi, K.-C., Kang, H.-B., Kim, H.-C., Lee, Y.-H., Haam, S., Park, H.-G., Yoon, H.-G.
(2008). Function of Multiple Lis-Homology Domain/WD-40 Repeat-Containing Proteins in Feed-Forward Transcriptional Repression by Silencing Mediator for Retinoic and Thyroid Receptor/Nuclear Receptor Corepressor Complexes. Mol. Endocrinol.
22: 1093-1104
[Abstract]
[Full Text]
-
Martinez, C. A., Arnosti, D. N.
(2008). Spreading of a Corepressor Linked to Action of Long-Range Repressor Hairy. Mol. Cell. Biol.
28: 2792-2802
[Abstract]
[Full Text]
-
Kelly, D. F., Lake, R. J., Walz, T., Artavanis-Tsakonas, S.
(2007). Conformational variability of the intracellular domain of Drosophila Notch and its interaction with Suppressor of Hairless. Proc. Natl. Acad. Sci. USA
104: 9591-9596
[Abstract]
[Full Text]
-
Guo, L., Han, A., Bates, D. L., Cao, J., Chen, L.
(2007). Crystal structure of a conserved N-terminal domain of histone deacetylase 4 reveals functional insights into glutamine-rich domains. Proc. Natl. Acad. Sci. USA
104: 4297-4302
[Abstract]
[Full Text]
-
Heimbucher, T., Murko, C., Bajoghli, B., Aghaallaei, N., Huber, A., Stebegg, R., Eberhard, D., Fink, M., Simeone, A., Czerny, T.
(2007). Gbx2 and Otx2 Interact with the WD40 Domain of Groucho/Tle Corepressors. Mol. Cell. Biol.
27: 340-351
[Abstract]
[Full Text]
-
Ratnaparkhi, G. S., Jia, S., Courey, A. J.
(2006). Uncoupling Dorsal-mediated activation from Dorsal-mediated repression in the Drosophila embryo. Development
133: 4409-4414
[Abstract]
[Full Text]
-
Marcal, N., Patel, H., Dong, Z., Belanger-Jasmin, S., Hoffman, B., Helgason, C. D., Dang, J., Stifani, S.
(2005). Antagonistic Effects of Grg6 and Groucho/TLE on the Transcription Repression Activity of Brain Factor 1/FoxG1 and Cortical Neuron Differentiation. Mol. Cell. Biol.
25: 10916-10929
[Abstract]
[Full Text]
-
Struffi, P., Arnosti, D. N.
(2005). Functional Interaction between the Drosophila Knirps Short Range Transcriptional Repressor and RPD3 Histone Deacetylase. J. Biol. Chem.
280: 40757-40765
[Abstract]
[Full Text]
-
Nagel, A. C., Krejci, A., Tenin, G., Bravo-Patino, A., Bray, S., Maier, D., Preiss, A.
(2005). Hairless-Mediated Repression of Notch Target Genes Requires the Combined Activity of Groucho and CtBP Corepressors. Mol. Cell. Biol.
25: 10433-10441
[Abstract]
[Full Text]
-
Choi, C. Y., Kim, Y. H., Kim, Y.-O., Park, S. J., Kim, E.-A, Riemenschneider, W., Gajewski, K., Schulz, R. A., Kim, Y.
(2005). Phosphorylation by the DHIPK2 Protein Kinase Modulates the Corepressor Activity of Groucho. J. Biol. Chem.
280: 21427-21436
[Abstract]
[Full Text]
-
Kulkarni, M. M., Arnosti, D. N.
(2005). cis-Regulatory Logic of Short-Range Transcriptional Repression in Drosophila melanogaster. Mol. Cell. Biol.
25: 3411-3420
[Abstract]
[Full Text]
Copyright © 2004 by the American Society for Microbiology. All rights reserved.