title: ELL Protein-associated Factor 2 (EAF2) Inhibits Transforming Growth Factor β Signaling through a Direct Interaction with Smad3.
abstract: A series of in vitro and in vivo studies has shown that EAF2 can affect multiple signaling pathways involved in cellular processes. However, the molecular mechanisms underlying its effects have remained elusive. Here we report the discovery of a new functional link between EAF2 and TGF-β signaling. Promoter reporter assays indicated that EAF2 suppresses Smad3 transcriptional activity, resulting in inhibition of TGF-β signaling. Coimmunoprecipitation assays showed that EAF2 specifically interacts with Smad3 in vitro and in vivo but not with other Smad proteins. In addition, we observed that EAF2 binding does not alter Smad3 phosphorylation but causes Smad3 cytoplasmic retention, competes with Smad4 for binding to Smad3, and prevents p300-Smad3 complex formation. Furthermore, we demonstrated that EAF2 suppresses both TGF-β-induced G1 cell cycle arrest and TGF-β-induced cell migration. This study identifies and characterizes a novel repressor of TGF-β signaling.
authors.affiliation: From the Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: From the Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China, Department of Reproduction, Maternal and Child Health Hospital of Hubei Province, Wuhan 430070, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: From the Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ouyang
authors.affiliation: Hubei University of Science and Technology, Xianning 437100, China, and.
authors.forename: Tieshan
authors.initials: T
authors.lastname: Song
authors.affiliation: Department of Urology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Huageng
authors.initials: H
authors.lastname: Liang
authors.affiliation: From the Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: From the Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China, w-xiao@ihb.ac.cn.
authors.forename: Wuhan
authors.initials: W
authors.lastname: Xiao
mesh_terms: D059447:Cell Cycle Checkpoints; D002460:Cell Line; D002465:Cell Movement; D006801:Humans; D011485:Protein Binding; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism*; D051901:Smad4 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: C472771:EAF2 protein, human; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051900:Smad3 Protein; D051901:Smad4 Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D050880:p300-CBP Transcription Factors
keywords: SMAD transcription factor; gene regulation; nuclear translocation; signal transduction; transforming growth factor β (TGF-B)