Drosophila Tcf and Groucho interact to repress Wingless signalling activity
Abstract
Wingless/Wnt signalling directs cell-fate choices during embryonic development. Inappropriate reactivation of the pathway causes cancer. In Drosophila, signal transduction from Wingless stabilizes cytosolic Armadillo, which then forms a bipartite transcription factor with the HMG-box protein Drosophila Tcf (dTcf) and activates expression of Wingless-responsive genes. Here we report that in the absence of Armadillo, dTcf acts as a transcriptional repressor of Wingless-responsive genes, and we show that Groucho acts as a corepressor in this process. Reduction of dTcf activity partially suppresses wingless and armadillo mutant phenotypes, leading to derepression of Wingless-responsive genes. Furthermore, overexpression of wild-type dTcf enhances the phenotype of a weak wingless allele. Finally, mutations in the Drosophila groucho gene also suppress wingless and armadillo mutant phenotypes as Groucho physically interacts with dTcf and is required for its full repressor activity.
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There is much cross-talk between the Hedgehog/Smoothened pathway and the Wnt pathway through GSK-3β and casein kinase I.
“there is much cross-talk with the Wnt pathway through GSK-3β and casein kinase I (115–118)”
From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [115]
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- Authors
- Cavallo, R. A., Cox, R. T., Moline, M. M., Roose, J., Polevoy, G. A., Clevers, H., Peifer, M., & Bejsovec, A.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Northwestern University (US)
- Corresponding author
- Bejsovec, Amy
- Venue
- Nature
- Published
- 1998-10
- Volume
- 395
- Issue
- 6702
- Pages
- 604-608
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2152123530
- Cited by
- 730
- References
- 27
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 4 · 2023: 12 · 2022: 19 · 2021: 16 · 2020: 16 · 2019: 23 · 2018: 17 · 2017: 30 · 2016: 12 · 2015: 18 · 2014: 31 · 2013: 20 · 2012: 30
- FWCI
- 15.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Keywords
- Groucho, Wingless signalling, Wnt signaling, armadillos, transcriptional repression, corepressors, transcriptional repressor, cell fate specification, wing development, protein-protein interaction
- MeSH terms
- Animals, DNA-Binding Proteins, Drosophila, High Mobility Group Proteins, Protein Binding, Proto-Oncogene Proteins, Repressor Proteins, Transcription Factors, Signal Transduction, Trans-Activators, Insect Proteins, COS Cells, Drosophila Proteins, Wnt1 Protein, Armadillo Domain Proteins, Basic Helix-Loop-Helix Proteins
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