title: DEDD negatively regulates transforming growth factor-beta1 signaling by interacting with Smad3.
abstract: 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.
authors.affiliation: Molecular Immunology and Pharmacology Laboratory, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Jian-Fei
authors.initials: JF
authors.lastname: Xue
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.forename: Qi
authors.initials: Q
authors.lastname: Lv
authors.forename: Heng
authors.initials: H
authors.lastname: Lin
authors.forename: Zi-Yan
authors.initials: ZY
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Jin-Wen
authors.initials: JW
authors.lastname: Liu
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Lv
authors.forename: Hong-Zhen
authors.initials: HZ
authors.lastname: Yang
authors.forename: Zhuo-Wei
authors.initials: ZW
authors.lastname: Hu
mesh_terms: 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*
chemical_list: C116096:DEDD protein, human; D004268:DNA-Binding Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; D053773:Transforming Growth Factor beta1