title: Fine-tuning of nuclear-catenin by Chibby and 14-3-3.
abstract: 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.
authors.affiliation: Department of Pharmacological Sciences, SUNY at Stony Brook, Stony Brook, New York 11794-8651, USA. takemaru@pharm.stonybrook.edu
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takemaru
authors.forename: Victoria
authors.initials: V
authors.lastname: Fischer
authors.forename: Feng-Qian
authors.initials: FQ
authors.lastname: Li
mesh_terms: 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
chemical_list: D048948:14-3-3 Proteins; D051177:Catenins; D009687:Nuclear Proteins; D051153:Wnt Proteins; D051057:Proto-Oncogene Proteins c-akt