Fine-tuning of nuclear-catenin by chibby and 14-3-3

Chibby (Cby) is an evolutionarily conserved antagonist of β-catenin, a central player of the canonical Wnt signaling pathway, which acts as a transcriptional coactivator. Cby physically interacts with the C-terminal activation domain of β-catenin and blocks its transcriptional activation potential through competition with DNA-binding Tcf/Lef transcription factors. Our recent study revealed a second mechanism for Cby-mediated β-catenin inhibition in which Cby cooperates with 14-3-3 adaptor proteins to facilitate nuclear export of β-catenin, following phosphorylation of Cby by Akt kinase. Therefore, our findings unravel a novel molecular mechanism regulating the dynamic nucleo-cytoplasmic trafficking of β-catenin and provide new insights into the crosstalk between the Wnt and Akt signaling pathways. Here, we review recent literature concerning Cby function and discuss our current understanding of the relationship between Wnt and Akt signaling.