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

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