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Regulation of transforming growth factor-β signaling by protein inhibitor of activated STAT, PIASy through Smad3.

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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)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 松田 正

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