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Regulation of transforming growth factor-β signaling by protein inhibitor of activated STAT, PIASy through Smad3.
| Title: | Regulation of transforming growth factor-β signaling by protein inhibitor of activated STAT, PIASy through Smad3. |
| Other Titles: | Regulation of TGF-β Signaling by Protein Inhibitor Activated of STAT, PIASy through Smad3 |
| Authors: | Imoto, Seiyu Browse this author | | Sugiyama, Kenji Browse this author | | Muromoto, Ryuta Browse this author | | Sato, Noriko Browse this author | | Yamamoto, Tetsuya Browse this author | | Matsuda, Tadashi Browse this author |
| Issue Date: | 5-Sep-2003 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 278 |
| Issue: | 36 |
| Start Page: | 34253 |
| End Page: | 34258 |
| Publisher DOI: | 10.1074/jbc.M304961200 |
| PMID: | 12815042 |
| Abstract: | Smads proteins play a key role in the intracellular signaling of the transforming growth factor (TGF)-β family of growth factors, which exhibits a diverse set of cellular responses, including cell proliferation and differentiation. In particular, Smad7 acts as an antagonist of TGF-β signaling, which could determine the intensity or duration of its signaling cascade. In this study we identified a protein inhibitor of activated STAT (signal transducers and activators of transcription), PIASy, as a novel interaction partner of Smad7 by yeast two-hybrid screening using the MH2 domain of Smad7 as bait. The association of Smad7 and PIASy was confirmed using co-expressed tagged proteins in 293T cells. Moreover, we found that other Smads including Smad3 also associated with PIASy through its MH2 domain, and PIASy suppressed TGF-β-mediated activation of Smad3. PIASy also stimulated the sumoylation of Smad3 in vivo. Furthermore, endogenous PIASy expression was induced by TGF-β in Hep3B cells. These findings provide the first evidence that a PIAS family protein, PIASy, associates with Smads and involves the regulation of TGF-β signaling using the negative feedback loop. |
| Rights: | Copyright © 2003 by the American Society for Biochemistry and Molecular Biology |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/28123 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 正
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