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つくばリポジトリ (Tulips-R) >
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Molecular biology of the cell >
Please use this identifier to cite or link to this item:
http://hdl.handle.net/2241/100062
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| Title: | Interaction with Smad4 Is Indispensable for Suppression of BMP Signaling by c-Ski |
| Authors: | Takeda, Masafumi
Mizuide, Masafumi
Oka, Masako
Watabe, Tetsuro
Inoue, Hirofumi
Suzuki, Hiroyuki
Fujita, Toshiro
Imamura, Takeshi
Miyazono, Kohei
Miyazawa, Keiji
鈴木, 裕之 |
| Issue Date: | Mar-2004 |
| Publisher: | American Society for Cell Biology |
| Journal Title: | Molecular biology of the cell |
| Volume: | 15 |
| Issue: | 3 |
| Start Page: | 963 |
| End Page: | 972 |
| DOI: | 10.1091/mbc.E03-07-0478 |
| PMID: | 14699069 |
| Abstract: | c-Ski is a transcriptional corepressor that interacts strongly with Smad2, Smad3, and Smad4 but only weakly with Smad1 and Smad5. Through binding to Smad proteins, c-Ski suppresses signaling of transforming growth factor-{beta} (TGF-{beta}) as well as bone morphogenetic proteins (BMPs). In the present study, we found that a mutant of c-Ski, termed c-Ski (ARPG) inhibited TGF-{beta}/activin signaling but not BMP signaling. Selectivity was confirmed in luciferase reporter assays and by determination of cellular responses in mammalian cells (BMP-induced osteoblastic differentiation of C2C12 cells and TGF-{beta}–induced epithelial-to-mesenchymal transdifferentiation of NMuMG cells) and Xenopus embryos. The ARPG mutant recruited histone deacetylases 1 (HDAC1) to the Smad3-Smad4 complex but not to the Smad1/5-Smad4 complex. c-Ski (ARPG) was unable to interact with Smad4, and the selective loss of suppression of BMP signaling by c-Ski (ARPG) was attributed to the lack of Smad4 binding. We also found that c-Ski interacted with Smad3 or Smad4 without disrupting Smad3-Smad4 heteromer formation. c-Ski (ARPG) would be useful for selectively suppressing TGF-{beta}/activin signaling. |
| URI: | http://hdl.handle.net/2241/100062 |
| Rights: | © 2004 by The American Society for Cell Biology |
| Text Version: | publisher |
| Appears in Collections: | Molecular biology of the cell
鈴木 裕之 (Suzuki Hiroyuki)
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