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All Tcf HMG box transcription factors interact with Groucho-related co-repressors
Open accessAbstract
Tcf/Lef family transcription factors are the downstream effectors of the Wingless/Wnt signal transduction pathway. Upon Wingless/Wnt signalling, beta-catenin translocates to the nucleus, interacts with Tcf (1-3) and thus activates transcription of target genes (4,5). Tcf factors also interact with members of the Groucho (Grg/TLE) family of transcriptional co-repressors (6). We have now tested all known mammalian Groucho family members for their ability to interact specifically with individual Tcf/Lef family members. Transcriptional activation by any Tcf could be repressed by Grg-1, Grg-2/TLE-2, Grg-3 and Grg-4 in a reporter assay. Specific interactions between Tcf and Grg proteins may be achieved in vivo by tissue- or cell type-limited expression. To address this, we determined the expression of all Tcf and Grg/TLE family members in a panel of cell lines. Within any cell line, several Tcfs and TLEs are co-expressed. Thus, redundancy in Tcf/Grg interactions appears to be the rule. The 'long' Groucho family members containing five domains are repressors of Tcf-mediated transactivation, whereas Grg-5, which only contains the first two domains, acts as a de-repressor. As previously shown for Drosophila Groucho, we show that long Grg proteins interact with histone deacetylase-1. Although Grg-5 contains the GP homology domain that mediates HDAC binding in long Grg proteins, Grg-5 fails to bind this co-repressor, explaining how it can de-repress transcription.
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Functional interaction of β-catenin with the transcription factor LEF-1
Behrens, J., von Kries, J. P., Kühl, M., Bruhn, L., Wedlich, D., Grosschedl, R., & Birchmeier, W. (1996) · Nature · doi:10.1038/382638a0 · Cited by 2,912
Conversion of Dorsal from an activator to a repressor by the global corepressor Groucho
Dubnicoff, T., Valentine, S. A., Chen, G., Shi, T., Lengyel, J. A., Paroush, Z., & Courey, A. J. (1997) · Genes & Development · doi:10.1101/gad.11.22.2952 · Cited by 155
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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
The MAGIC investigators, Voight, B. F., The GIANT Consortium, Scott, L. J., Steinthorsdottir, V., Morris, A. P., Dina, C., Welch, R. P., Zeggini, E., Huth, C., et al. (2010) · Nature Genetics · doi:10.1038/ng.609 · Cited by 1,761
Caught up in a Wnt storm: Wnt signaling in cancer
Giles, R. H., van Es, J. H., & Clevers, H. (2003) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(03)00005-2 · Cited by 1,482
TCF/LEFs and Wnt Signaling in the Nucleus
Cadigan, K. M., & Waterman, M. L. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a007906 · Cited by 760
HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the β-catenin–TCF interaction
Ye, F., Chen, Y., Hoang, T., Montgomery, R. L., Zhao, X.-H., Bu, H., Hu, T., Taketo, M. M., van Es, J. H., Clevers, H., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2333 · Cited by 559
Diversity of LEF/TCF action in development and disease
Arce, L., Yokoyama, N. N., & Waterman, M. L. (2006) · Oncogene · doi:10.1038/sj.onc.1210056 · Cited by 438
Metadata
- Authors
- Brantjes, H.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-04-01
- Volume
- 29
- Issue
- 7
- Pages
- 1410-1419
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2007717461
- Cited by
- 361
- References
- 2
- FWCI
- 6.62
- Type
- journal article
- Language
- en
- Open access
- green
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