ZFIN ID: ZDB-PUB-170910-4
Transcriptional factors Eaf1/2 inhibit endoderm and mesoderm formation via suppressing TGF-β signaling
Liu, J.X., Xu, Q.H., Li, S., Yu, X., Liu, W., Ouyang, G., Zhang, T., Chen, L.L.
Date: 2017
Source: Biochimica et biophysica acta   1860(10): 1103-1116 (Journal)
Registered Authors: Liu, Jing-xia, Ouyang, Gang
Keywords: Eaf1/2, Endoderm, Mesoderm, P53, TGF-β
MeSH Terms:
  • Amino Acid Substitution
  • Animals
  • Endoderm/embryology*
  • Mesoderm/embryology*
  • Mutation, Missense
  • Signal Transduction/physiology*
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/metabolism*
  • Tumor Suppressor Protein p53/genetics
  • Tumor Suppressor Protein p53/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 28887217 Full text @ Biochim. Biophys. Acta
Eaf family genes act in multiple cellular responses such as tumor suppression and embryonic development. In our previous work, Eaf1/2 was found to modulate convergence and extension (C&E) movements and pattern the embryonic anterior-posterior axis during zebrafish embryogenesis. Here, we found that loss-of-function of eaf1/2 caused expanded mesoderm and endoderm in zebrafish embryos and led to the recovery of endoderm specification in TGF-β factor-mzoeptz257 mutants, while gain-of-function of eaf1/2 induced reduced mesoderm and endoderm. Analyses of gene expression profiles in Eaf deleted or over-expressed mammalian cells indicated that the roles of Eaf1 and Eaf2 in inhibiting TGF-β signals were conserved from fish to mammals. By taking advantages of TGF-β reporters, eaf1/2-fused engrailed proteins, and P53M214K mutant, we revealed that Eaf1 and Eaf2 might suppress TGF-β transduction by synergistically inhibiting none-P53 and P53-required TGF-β signaling. Furthermore, Eaf1/2 might co-localize and interact with TGF-β transcriptional factors in the transcriptional complex as repressors to target and suppress TGF-β signaling activity. Our study unveiled a previously unrecognized link of Eaf1/2 genes with TGF-β and P53 in vertebrates and demonstrated a conservation of TGF-β suppression activity for Eaf1/2 family genes from fish to mammals, which might shed some light on the molecular mechanistic basis of Eaf1 and Eaf2 in tumor suppression.