ZFIN ID: ZDB-PUB-130211-12
Eaf1 and Eaf2 negatively regulate canonical Wnt/β-catenin signaling
Liu, J.X., Zhang, D., Xie, X., Ouyang, G., Liu, X., Sun, Y., and Xiao, W.
Date: 2013
Source: Development (Cambridge, England)   140(5): 1067-1078 (Journal)
Registered Authors: Liu, Jing-xia, Ouyang, Gang, Sun, Yonghua, Xiao, Wuhan, Xie, Xunwei
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Body Patterning/genetics
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cytoskeletal Proteins/genetics
  • Cytoskeletal Proteins/metabolism
  • Cytoskeletal Proteins/physiology
  • Down-Regulation/genetics
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • HEK293 Cells
  • Humans
  • Mice
  • Neural Plate/embryology
  • Neural Plate/metabolism
  • Wnt Proteins/genetics
  • Wnt Proteins/metabolism
  • Wnt Proteins/physiology
  • Wnt Signaling Pathway/genetics*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed: 23364330 Full text @ Development

Eaf factors play a crucial role in tumor suppression and embryogenesis. To investigate the potential mechanism of Eaf activity, we performed loss- and gain-of-function assays in zebrafish using morpholino and mRNA injections, respectively. We found that eaf1 and eaf2 inhibit Wnt/β-catenin signaling, thereby modulating mesodermal and neural patterning in the embryo. Moreover, ectopic expression of eaf1 and eaf2 in embryos and cultured cells blocked β-catenin reporter activity. By immunoprecipitation, we also observed that Eaf1 and Eaf2 bound to the Armadillo repeat region and C-terminus of β-catenin, as well as to other β-catenin transcription complex proteins, such as c-Jun, Tcf and Axin, suggesting the formation of a novel complex. In addition, the N-terminus of Eaf1 and Eaf2 bound to β-catenin and exhibited dominant-negative activity, whereas the C-terminus appeared to either harbor a suppression domain or to recruit a repressor. Both the N- and C-terminus must be intact for Eaf1 and Eaf2 suppressive activity. Lastly, we demonstrate a conservation of biological activities for Eaf family proteins across species. In summary, our evidence points to a novel role for Eaf1 and Eaf2 in inhibiting canonical Wnt/β-catenin signaling, which might form the mechanistic basis for Eaf1 and Eaf2 tumor suppressor activity.