FEBS Letters
Volume 584, Issue 14 , Pages 3028-3034, 16 July 2010

DEDD negatively regulates transforming growth factor-β1 signaling by interacting with Smad3

Edited by Zhijie Chang

Molecular Immunology and Pharmacology Laboratory, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xian Nong Tan St., Beijing 100050, People’s Republic of China

Received 30 March 2010; received in revised form 18 May 2010; accepted 19 May 2010. published online 28 May 2010.

Abstract 

Transforming growth factor-β1 (TGF-β1) 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-β1/Smad3-mediated transcription. DEDD inhibited the functions of Smad3 by preventing Smad3 phosphorylation, which led to the reduced expression of TGF-β1/Smad3-targeted genes. TGF-β1 inhibited DEDD expression, and DEDD inhibited TGF-β1-mediated invasion. Therefore, our findings suggest that through its interaction with Smad3, DEDD is a novel negative regulator of the TGF-β1 signaling pathway.

Structured summary

MINT-7895480: DEDD (uniprotkb:O75618) physically interacts (MI:0915) with Smad3 (uniprotkb:P84022) by anti bait co-immunoprecipitation (MI:0006)

Keywords: DEDD, Smad3, TGF-β1, Signal transduction, Cancer, Invasion

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PII: S0014-5793(10)00447-3

doi:10.1016/j.febslet.2010.05.043

FEBS Letters
Volume 584, Issue 14 , Pages 3028-3034, 16 July 2010

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