Functional interaction of β-catenin with the transcription factor LEF-1
Abstract
The cytoplasmic proteins beta-catenin of vertebrates and armadillo of Drosophila have two functions: they link the cadherin cell-adhesion molecules to the cytoskeleton, and they participate in the wnt/wingless signal pathway. Here we show, in a yeast two-hybrid screen, that the architectural transcription factor LEF-1 (for lymphoid enhancer-binding factor) interacts with beta-catenin. In mammalian cells, coexpressed LEF-1 and beta-catenin form a complex that is localized to the nucleus and can be detected by immunoprecipitation. Moreover, LEF-1 and beta-catenin form a ternary complex with DNA that splays an altered DNA bend. Microinjection of LEF-1 into XenoPus embryos induces axis duplication, which is augmented by interaction with beta-catenin. Thus beta-catenin regulates gene expression by direct interaction with transcription factors such as LEF-1, providing a molecular mechanism for the transmission of signals, from cell-adhesion components or wnt protein to the nucleus.
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LEF-1/TCF forms a complex with β-catenin in response to Wnt stimulation.
“LEF-1/TCF has been shown to form a complex with β-catenin in response to Wnt stimulation (2, 4, 18, 34).”
A small deletion removing the NH2-terminal 62 amino acids of LEF-1 (LEF-1ΔN) abrogates its interaction with β-catenin.
“A small deletion removing the NH2-terminal 62 amino acids of LEF-1 (LEF-1ΔN) abrogated its interaction with β-catenin (data not shown) (2).”
β-Catenin binds to a region within the NH2-terminal region of LEF-1/TCF.
“β-Catenin binds to a region within the NH2-terminal region of LEF-1/TCF (see Fig. 3A) (2).”
The β-catenin-LEF-1/TCF complex activates Wnt target genes in the nucleus.
“The β-catenin-LEF-1/TCF complex, in turn, activates Wnt target genes in the nucleus (2, 4, 18, 34).”
β-catenins can stably bind to LEF-1/TCF.
“On the other hand, β-catenins can stably bind to LEF-1/TCF (2).”
LEF-1 cooperizes with stabilized β-catenin to activate Wnt target genes.
“Supporting this, lymphoid enhancer‐binding factor‐1 was upregulated in endothelial cells, where it cooperizes with stabilized β‐catenin to activate Wnt target genes. 69”
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- Authors
- Behrens, J., von Kries, J. P., Kühl, M., Bruhn, L., Wedlich, D., Grosschedl, R., & Birchmeier, W.
- Affiliations
- Max Delbrück Center (DE)
- Universität Ulm (DE)
- Howard Hughes Medical Institute (US)
- Venue
- Nature
- Published
- 1996-08
- Volume
- 382
- Issue
- 6592
- Pages
- 638-642
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1989215255
- Cited by
- 2,912
- References
- 0
- Citations by year
- 2026: 28 · 2025: 43 · 2024: 43 · 2023: 58 · 2022: 58 · 2021: 79 · 2020: 70 · 2019: 73 · 2018: 72 · 2017: 67 · 2016: 78 · 2015: 73 · 2014: 102 · 2013: 93 · 2012: 118
- FWCI
- 55.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (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 › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- β-catenin, LEF1, transcription factor interaction, Wnt signaling, armadillos, DNA bending, axis duplication, signal transduction, gene expression regulation, Xenopus embryo
- MeSH terms
- Animals, Cell Line, Cell Nucleus, Cloning, Molecular, Cytoskeletal Proteins, DNA, DNA-Binding Proteins, Drosophila, Escherichia coli, Nucleic Acid Conformation, Protein Binding, Recombinant Proteins, RNA, Messenger, Saccharomyces cerevisiae, Transcription Factors, Xenopus, Trans-Activators, Cadherins, Xenopus Proteins, beta Catenin, Lymphoid Enhancer-Binding Factor 1
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