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Sumoylation of Smad3 stimulates its nuclear export during PIASy-mediated suppression of TGF-β signaling

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Title: Sumoylation of Smad3 stimulates its nuclear export during PIASy-mediated suppression of TGF-β signaling
Other Titles: Smad3 sumoylation regulates nuclear retention
Authors: Imoto, Seiyu Browse this author
Ohbayashi, Norihiko Browse this author
Ikeda, Osamu Browse this author
Kamitani, Shinya Browse this author
Muromoto, Ryuta Browse this author
Sekine, Yuichi Browse this author
Matsuda, Tadashi Browse this author →KAKEN DB
Keywords: Smad3
nuclear export
Issue Date: 30-May-2008
Publisher: Academic Press
Journal Title: Biochemical and Biophysical Research Communications
Volume: 370
Issue: 2
Start Page: 359
End Page: 365
Publisher DOI: 10.1016/j.bbrc.2008.03.116
PMID: 18384750
Abstract: Sma- and MAD-related protein 3 (Smad3) plays crucial roles in the transforming growth factor-β (TGF-β)-meditaed signaling pathway, which produce a variety of cellular responses, including cell proliferation and differentiation. In our previous study, we demonstrated that protein inhibitor of activated STATy (PIASy) suppresses TGF-βsignaling by interacting with and sumoylating Smad3. In the present study, we examined the molecular mechanisms of Smad3 sumoylation during PIASy-mediated suppression of TGF-βsignaling. We found that small-interfering RNA-mediated reduction of endogenous PIASy expression enhanced TGFβ- induced gene expression. Importantly, coexpression of Smad3 with PIASy and SUMO1 affected the DNA-binding activity of Smad3. Furthermore, coexpression of Smad3 with PIASy and SUMO1 stimulated the nuclear export of Smad3. Finally, fluorescence resonance energy transfer analyses revealed that Smad3 interacted with SUMO1 in the cytoplasm. These results suggest that PIASy regulates TGF-β/Smad3-mediated signaling by stimulating sumoylation and nuclear export of Smad3.
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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