Fine-tuning of nuclear-catenin by Chibby and 14-3-3.
Chibby (Cby) is an evolutionarily conserved antagonist of beta-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 beta-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 beta-catenin inhibition in which Cby cooperates with 14-3-3 adaptor proteins to facilitate nuclear export of beta-catenin, following phosphorylation of Cby by Akt kinase. Therefore, our findings unravel a novel molecular mechanism regulating the dynamic nucleo-cytoplasmic trafficking of beta-catenin and provide new insights into the cross-talk 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.
Takemaru
Ken-Ichi
K
Department of Pharmacological Sciences, SUNY at Stony Brook, Stony Brook, New York 11794-8651, USA. takemaru@pharm.stonybrook.edu
Fischer
Victoria
V
Li
Feng-Qian
FQ
D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D051177:Catenins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism
D048948:14-3-3 Proteins; D051177:Catenins; D009687:Nuclear Proteins; D051153:Wnt Proteins; D051057:Proto-Oncogene Proteins c-akt