Members of the Eaf gene family are involved in tumour suppression and in embryogenesis but what are the molecular mechanisms that underlie these activities? Here (), Wuhan Xiao and colleagues report that eaf1 and eaf2 modulate mesodermal and neural patterning in zebrafish embryos through inhibition of canonical Wnt/β-catenin signalling. They show that ectopic expression of eaf1 and eaf2 in zebrafish embryos and in cultured cells blocks β-catenin reporter activity. Furthermore, they show that Eaf1 and Eaf2 bind to the Armadillo repeat region and C-terminus of β-catenin, and to other β-catenin transcription complex proteins. Both the N- and C-terminus of Eaf1 and Eaf2 must be intact for their suppressive activity, they report. Finally, they show that the biological activities of Eaf family proteins are conserved across species. Together, these results identify a novel role for Eaf1 and Eaf2 in the inhibition of canonical Wnt/β-catenin signalling that might provide the mechanistic basis for the tumour suppressor activity of Eaf family proteins.
