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 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.
Xue
Jian-Fei
JF
Molecular Immunology and Pharmacology Laboratory, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
Hua
Fang
F
Lv
Qi
Q
Lin
Heng
H
Wang
Zi-Yan
ZY
Yan
Jun
J
Liu
Jin-Wen
JW
Lv
Xiao-Xi
XX
Yang
Hong-Zhen
HZ
Hu
Zhuo-Wei
ZW
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
C116096:DEDD protein, human; D004268:DNA-Binding Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; D053773:Transforming Growth Factor beta1