The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Smad7 Antagonizes Transforming Growth Factor β Signaling in the Nucleus by Interfering with Functional Smad-DNA Complex Formation
Open accessAbstract
Smad7 plays an essential role in the negative-feedback regulation of transforming growth factor beta (TGF-beta) signaling by inhibiting TGF-beta signaling at the receptor level. It can interfere with binding to type I receptors and thus activation of receptor-regulated Smads or recruit the E3 ubiquitin ligase Smurf to receptors and thus target them for degradation. Here, we report that Smad7 is predominantly localized in the nucleus of Hep3B cells. The targeted expression of Smad7 in the nucleus conferred superior inhibitory activity on TGF-beta signaling, as determined by reporter assay in mammalian cells and by its effect on zebrafish embryogenesis. Furthermore, Smad7 repressed Smad3/4-, Smad2/4-, and Smad1/4-enhanced reporter gene expression, indicating that Smad7 can function independently of type I receptors. An oligonucleotide precipitation assay revealed that Smad7 can specifically bind to the Smad-responsive element via its MH2 domain, and DNA-binding activity was further confirmed in vivo with the promoter of PAI-1, a TGF-beta target gene, by chromatin immunoprecipitation. Finally, we provide evidence that Smad7 disrupts the formation of the TGF-beta-induced functional Smad-DNA complex. Our findings suggest that Smad7 inhibits TGF-beta signaling in the nucleus by a novel mechanism.
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Cites
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Self-citationIdentification of Smad7, a TGFβ-inducible antagonist of TGF-β signalling
Nakao, A., Afrakhte, M., Morn, A., Nakayama, T., Christian, J. L., Heuchel, R., Itoh, S., Kawabata, M., Heldin, N.-E., Heldin, C.-H., et al. (1997) · Nature · doi:10.1038/39369 · Cited by 1,809
Cited by
TGF-β and BMP Signaling in Osteoblast Differentiation and Bone Formation
Chen, G., Deng, C., & Li, Y.-P. (2012) · International Journal of Biological Sciences · doi:10.7150/ijbs.2929 · Cited by 1,756
The regulation of TGFβ signal transduction
Moustakas, A., & Heldin, C.-H. (2009) · Development · doi:10.1242/dev.030338 · Cited by 832
Specificity, versatility, and control of TGF-β family signaling
Derynck, R., & Budi, E. H. (2019) · Science Signaling · doi:10.1126/scisignal.aav5183 · Cited by 785
Regulation of TGF-β Family Signaling by Inhibitory Smads
Miyazawa, K., & Miyazono, K. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022095 · Cited by 439
Targeting TGFβ signal transduction for cancer therapy
Liu, S., Ren, J., & ten Dijke, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00436-9 · Cited by 413
“SMAD7 can also antagonize TGFβ signaling in the nucleus by disrupting the formation of the functional SMAD–DNA complex.(60,61) Moreover, SMAD7 recruits E3 ubiquitin ligases such as SMAD ubiquitination regulatory factor 1/2 (SMURF1/2), WW domain-containing protein 1 (WWP1), and neural precursor cellexpressed developmen…”
Background
Metadata
- Authors
- Zhang, S., Fei, T., Zhang, L., Zhang, R., Chen, F., Ning, Y., Han, Y., Feng, X.-H., Meng, A., & Chen, Y.-G.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2007-06-01
- Volume
- 27
- Issue
- 12
- Pages
- 4488-4499
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2128827916
- Cited by
- 255
- References
- 59
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Smad7 Antagonizes Transforming Growth Factor β Signaling in the Nucleus by Interfering with Functional Smad-DNA Complex Formation. https://app.cochat.ai/papers/10.1128/mcb.01636-06
- The paper
- Zhang, S., Fei, T., Zhang, L., Zhang, R., Chen, F., Ning, Y., Han, Y., Feng, X.-H., Meng, A., & Chen, Y.-G. (2007). Smad7 Antagonizes Transforming Growth Factor β Signaling in the Nucleus by Interfering with Functional Smad-DNA Complex Formation. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.01636-06
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