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Disruption of Transforming Growth Factor-β Signaling in ELF β-Spectrin-Deficient Mice
Abstract
Disruption of the adaptor protein ELF, a β-spectrin, leads to disruption of transforming growth factor–β (TGF-β) signaling by Smad proteins in mice. Elf −/− mice exhibit a phenotype similar to smad2 +/− / smad3 +/− mutant mice of midgestational death due to gastrointestinal, liver, neural, and heart defects. We show that TGF-β triggers phosphorylation and association of ELF with Smad3 and Smad4, followed by nuclear translocation. ELF deficiency results in mislocalization of Smad3 and Smad4 and loss of the TGF-β–dependent transcriptional response, which could be rescued by overexpression of the COOH-terminal region of ELF. This study reveals an unexpected molecular link between a major dynamic scaffolding protein and a key signaling pathway.
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Cites
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
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Yingling, J. M., Blanchard, K. L., & Sawyer, J. S. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1580 · Cited by 549
Actions of TGF-β as tumor suppressor and pro-metastatic factor in human cancer
Pardali, K., & Moustakas, A. (2007) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2006.06.004 · Cited by 526
The transforming growth factor-β superfamily of receptors
de Caestecker, M. (2004) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2003.10.004 · Cited by 464
Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview
Wang, L.-H., Wu, C.-F., Rajasekaran, N., & Shin, Y. K. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000495956 · Cited by 334
Liver development update: new embryo models, cell lineage control, and morphogenesis
Lemaigre, F., & Zaret, K. S. (2004) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2004.08.004 · Cited by 288
Metadata
- Authors
- Tang, Y., Katuri, V., Dillner, A., Mishra, B., Deng, C.-X., & Mishra, L.
- Venue
- Science
- Published
- 2003-01-24
- Volume
- 299
- Issue
- 5606
- Pages
- 574-577
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1633357948
- Cited by
- 262
- References
- 1
- FWCI
- 5.15
- Type
- journal article
- Language
- en
- Open access
- closed
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- Tang, Y., Katuri, V., Dillner, A., Mishra, B., Deng, C.-X., & Mishra, L. (2003). Disruption of Transforming Growth Factor-β Signaling in ELF β-Spectrin-Deficient Mice. Science. https://doi.org/10.1126/science.1075994
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
