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

被引：61

作者：

Imoto, Seiyu ^{[1
]}

Ohbayashi, Norihiko ^{[1
]}

Ikeda, Osamu ^{[1
]}

Kamitani, Shinya ^{[1
]}

Muromoto, Ryuta ^{[1
]}

Sekine, Yuichi ^{[1
]}

Matsuda, Tadashi ^{[1
]}

机构：

[1] Hokkaido Univ, Grad Sch Pharmaceut Sci, Dept Immunol, Kita Ku, Sapporo, Hokkaido 0600812, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 370卷 / 02期

关键词：

Smad3; TGF-beta; PIASy; sumoylation; nuclear export;

D O I：

10.1016/j.bbrc.2008.03.116

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Sma- and MAD-related protein 3 (Smad3) plays crucial roles in the transforming growth factor-beta(TGF-beta)-mediated 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-beta signaling by interacting with and sumoylating Smad3. In the present study, we examined the molecular mechanisms of Smad3 sumoylation during PIASy-mediated suppression of TGF-beta signaling. We found that small-interfering RNA-mediated reduction of endogenous PIASy expression enhanced TGF-beta-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-beta/Smad3-mediated signaling by stimulating sumoylation and nuclear export of Smad3. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：359 / 365

页数：7

共 26 条

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