HIC1 attenuates Wnt signaling by recruitment of TCF-4 and beta-catenin to the nuclear bodies
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16724116
PubMed Central
PMC1478201
DOI
10.1038/sj.emboj.7601147
PII: 7601147
Knihovny.cz E-resources
- MeSH
- Axin Protein MeSH
- beta Catenin genetics metabolism MeSH
- Cell Nucleus metabolism MeSH
- Cytoskeletal Proteins genetics metabolism MeSH
- DNA-Binding Proteins genetics metabolism MeSH
- Transcription, Genetic MeSH
- Culture Media, Conditioned MeSH
- Humans MeSH
- Mice MeSH
- Promoter Regions, Genetic MeSH
- Transcription Factor 7-Like 2 Protein MeSH
- Wnt Proteins genetics metabolism MeSH
- Gene Expression Regulation MeSH
- RNA Interference MeSH
- Signal Transduction physiology MeSH
- Kruppel-Like Transcription Factors MeSH
- TCF Transcription Factors genetics metabolism MeSH
- Transcription Factors genetics metabolism MeSH
- Protein Binding MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Axin Protein MeSH
- AXIN2 protein, human MeSH Browser
- beta Catenin MeSH
- Cytoskeletal Proteins MeSH
- DNA-Binding Proteins MeSH
- HIC1 protein, human MeSH Browser
- Culture Media, Conditioned MeSH
- Transcription Factor 7-Like 2 Protein MeSH
- Wnt Proteins MeSH
- TCF7L2 protein, human MeSH Browser
- Tcf7l2 protein, mouse MeSH Browser
- Kruppel-Like Transcription Factors MeSH
- TCF Transcription Factors MeSH
- Transcription Factors MeSH
The hypermethylated in cancer 1 (HIC1) gene is epigenetically inactivated in cancer, and in addition, the haploinsufficiency of HIC1 is linked to the development of human Miller-Dieker syndrome. HIC1 encodes a zinc-finger transcription factor that acts as a transcriptional repressor. Additionally, the HIC1 protein oligomerizes via the N-terminal BTB/POZ domain and forms discrete nuclear structures known as HIC1 bodies. Here, we provide evidence that HIC1 antagonizes the TCF/beta-catenin-mediated transcription in Wnt-stimulated cells. This appears to be due to the ability of HIC1 to associate with TCF-4 and to recruit TCF-4 and beta-catenin to the HIC1 bodies. As a result of the recruitment, both proteins are prevented from association with the TCF-binding elements of the Wnt-responsive genes. These data indicate that the intracellular amounts of HIC1 protein can modulate the level of the transcriptional stimulation of the genes regulated by canonical Wnt/beta-catenin signaling.
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