Sumoylation of Smad3 stimulates its nuclear export during PIASy-mediated suppression of TGF-β signaling
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概要
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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.
- Academic Pressの論文
- 2008-05-30
著者
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Shimoda K
Department Of Internal Medicine Gastroenterology And Hematology Faculty Of Medicine Miyazaki Univers
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Shimoda Kazuya
九州大学 医学部病態情報学
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Shimoda Kazuya
九州大学 第1内科
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OHBAYASHI Norihiko
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University
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IMOTO Seiyu
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University
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Muromoto Ryuta
Department Of Immunology Graduate School Of Pharmaceutical Sciences Hokkaido University
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Imoto Seiyu
Department Of Immunology Graduate School Of Pharmaceutical Sciences Hokkaido University
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Imoto Seiyu
北海道大学 大学院薬学研究科
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Shimoda Kazuya
Medicine And Biosystemic Science Graduate School Of Medical Sciences Kyushu University
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Sekine Yuichi
Department Of Immunology Graduate School Of Pharmaceutical Sciences Hokkaido University
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Matsuda Tadashi
Department Of Immunology Graduate School Of Pharmaceutical Sciences Hokkaido University
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Ohbayashi Norihiko
Department Of Immunology Graduate School Of Pharmaceutical Sciences Hokkaido University
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Sugiyama Kenji
Department Of Internal Medicine Gastroenterology And Hematology Faculty Of Medicine Miyazaki Univers
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Sugio Y
Miyazaki Prefectural Miyazaki Hospital Miyazaki Jpn
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Ikeda Osamu
Department Of Immunology Graduate School Of Pharmaceutical Sciences Hokkaido University
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