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c-Ski Acts as a Transcriptional Co-repressor in Transforming Growth Factor-β Signaling through Interaction with Smads
Open accessAbstract
Smads are intracellular signaling mediators of the transforming growth factor-beta (TGF-beta) superfamily that regulates a wide variety of biological processes. Among them, Smads 2 and 3 are activated specifically by TGF-beta. We identified c-Ski as a Smad2 interacting protein. c-Ski is the cellular homologue of the v-ski oncogene product and has been shown to repress transcription by recruiting histone deacetylase (HDAC). Smad2/3 interacts with c-Ski through its C-terminal MH2 domain in a TGF-beta-dependent manner. c-Ski contains two distinct Smad-binding sites with different binding properties. c-Ski strongly inhibits transactivation of various reporter genes by TGF-beta. c-Ski is incorporated in the Smad DNA binding complex, interferes with the interaction of Smad3 with a transcriptional co-activator, p300, and in turn recruits HDAC. c-Ski is thus a transcriptional co-repressor that links Smads to HDAC in TGF-beta signaling.
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Cites
Three proteins define a class of human histone deacetylases related to yeast Hda1p
Grozinger, C. M., Hassig, C. A., & Schreiber, S. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.9.4868 · Cited by 770
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Lee, S.-J. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.012103.135836 · Cited by 819
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Metadata
- Authors
- Akiyoshi, S., Inoue, H., Hanai, J.-I., Kusanagi, K., Nemoto, N., Miyazono, K., & Kawabata, M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-12
- Volume
- 274
- Issue
- 49
- Pages
- 35269-35277
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2015441766
- Cited by
- 373
- References
- 1
- FWCI
- 9.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: c-Ski Acts as a Transcriptional Co-repressor in Transforming Growth Factor-β Signaling through Interaction with Smads. https://app.cochat.ai/papers/10.1074/jbc.274.49.35269
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- Akiyoshi, S., Inoue, H., Hanai, J.-I., Kusanagi, K., Nemoto, N., Miyazono, K., & Kawabata, M. (1999). c-Ski Acts as a Transcriptional Co-repressor in Transforming Growth Factor-β Signaling through Interaction with Smads. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.49.35269
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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