DEDD negatively regulates transforming growth factor-beta1 signaling by interacting with Smad3

Transforming growth factor-beta1 (TGF-beta1) regulates a wide variety of cellular responses, such as proliferation, differentiation, migration and apoptosis. Here we report that death effector domain-containing DNA-binding protein (DEDD) physically interacts with Smad3. The inhibition of Smad3 by DE...

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Published inFEBS letters Vol. 584; no. 14; pp. 3028 - 3034
Main Authors Xue, Jian-Fei, Hua, Fang, Lv, Qi, Lin, Heng, Wang, Zi-Yan, Yan, Jun, Liu, Jin-Wen, Lv, Xiao-Xi, Yang, Hong-Zhen, Hu, Zhuo-Wei
Format Journal Article
LanguageEnglish
Published England 16.07.2010
Subjects
Animals
Apoptosis - genetics
Cell Differentiation - genetics
Death Domain Receptor Signaling Adaptor Proteins
DNA-Binding Proteins
Mice
Phosphorylation
Signal Transduction - genetics
Signal Transduction - physiology
Transforming Growth Factor beta1 - genetics
Transforming Growth Factor beta1 - metabolism
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Summary:Transforming growth factor-beta1 (TGF-beta1) regulates a wide variety of cellular responses, such as proliferation, differentiation, migration and apoptosis. Here we report that death effector domain-containing DNA-binding protein (DEDD) physically interacts with Smad3. The inhibition of Smad3 by DEDD resulted in a reduction in TGF-beta1/Smad3-mediated transcription. DEDD inhibited the functions of Smad3 by preventing Smad3 phosphorylation, which led to the reduced expression of TGF-beta1/Smad3-targeted genes. TGF-beta1 inhibited DEDD expression, and DEDD inhibited TGF-beta1-mediated invasion. Therefore, our findings suggest that through its interaction with Smad3, DEDD is a novel negative regulator of the TGF-beta1 signaling pathway.
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ISSN:1873-3468
DOI:10.1016/j.febslet.2010.05.043