Eaf1 and Eaf2 negatively regulate canonical Wnt/β-catenin signaling
- Authors
- Liu, J.X., Zhang, D., Xie, X., Ouyang, G., Liu, X., Sun, Y., and Xiao, W.
- ID
- ZDB-PUB-130211-12
- 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.