The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-β and Wnt pathways
Open accessAbstract
The transforming growth factor-β (TGFβ) and Wnt/wingless pathways play pivotal roles in tissue specification during development. Activation of Smads, the effectors of TGFβ superfamily signals, results in Smad translocation from the cytoplasm into the nucleus where they act as transcriptional comodulators to regulate target gene expression. Wnt/wingless signals are mediated by the DNA-binding HMG box transcription factors lymphoid enhancer binding factor 1/T cell-specific factor (LEF1/TCF) and their coactivator β-catenin. Herein, we show that Smad3 physically interacts with the HMG box domain of LEF1 and that TGFβ and Wnt pathways synergize to activate transcription of the Xenopus homeobox gene twin ( Xtwn ). Disruption of specific Smad and LEF1/TCF DNA-binding sites in the promoter abrogates synergistic activation of the promoter. Consistent with this observation, introduction of Smad sites into a TGFβ-insensitive LEF1/TCF target gene confers cooperative TGFβ and Wnt responsiveness to the promoter. Furthermore, we demonstrate that TGFβ-dependent activation of LEF1/TCF target genes can occur in the absence of β-catenin binding to LEF1/TCF and requires both Smad and LEF1/TCF DNA-binding sites in the Xtwn promoter. Thus, our results show that TGFβ and Wnt signaling pathways can independently or cooperatively regulate LEF1/TCF target genes and suggest a model for how these pathways can synergistically activate target genes.
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Cites
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TGF-β signalling from cell membrane to nucleus through SMAD proteins
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Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon Carcinoma
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Somatic mutations of the β-catenin gene are frequent in mouse and human hepatocellular carcinomas
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Transcriptional Activators of TGF-β Responses: Smads
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Self-citationRegulation of LEF-1/TCF transcription factors by Wnt and other signals
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Smads as transcriptional co-modulators
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Cited by
Massagué, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3434 · Cited by 3,128
TGFβ Signaling in Growth Control, Cancer, and Heritable Disorders
Massagué, J., Blain, S. W., & Lo, R. S. (2000) · Cell · doi:10.1016/s0092-8674(00)00121-5 · Cited by 2,385
TGF-β Signaling in Tumor Suppression and Cancer Progression
Derynck, R., Akhurst, R. J., & Balmain, A. (2001) · Nature Genetics · doi:10.1038/ng1001-117 · Cited by 2,275
Massagué, J. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35043051 · Cited by 1,899
SPECIFICITY AND VERSATILITY IN TGF-β SIGNALING THROUGH SMADS
Feng, X.-H., & Derynck, R. (2005) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.21.022404.142018 · Cited by 1,869
Metadata
- Authors
- Labbé, E., Letamendia, A., & Attisano, L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2000-07-11
- Volume
- 97
- Issue
- 15
- Pages
- 8358-8363
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2059030354
- Cited by
- 440
- References
- 22
- FWCI
- 8.00
- Type
- journal article
- Language
- en
- Open access
- green
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- Labbé, E., Letamendia, A., & Attisano, L. (2000). Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-β and Wnt pathways. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.150152697
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