Transactivation activity and nucleocytoplasmic transport of β-catenin are independently regulated by its C-terminal end.

Abstract

The key protein in the canonical Wnt pathway is β-catenin, which is phosphorylated both in absence and presence of Wnt signals by different kinases. Upon activation in the cytoplasm, β-catenin can enter into the nucleus to transactivate target gene expression, many of which are cancer-related genes. The mechanism governing β-catenin's nucleocytoplasmic transport has been recently unvealed, although phosphorylation at its C-terminal end and its functional consequences are not completely understood. Serine 646 of β-catenin is a putative CK2 phosphorylation site and lies in a region which has been proposed to be important for its nucleocytoplasmic transport and transactivation activity. This residue was mutated to aspartic acid mimicking CK2-phosphorylation and its effects on β-catenin activity as well as localization were explored. β-Catenin S6464D did not show significant differences in both transcriptional activity and nuclear localization compared to the wild-type form, but displayed a characteristic granular nuclear pattern. Three-dimensional models of nuclei were constructed which showed differences in number and volume of granules, being those from β-catenin S646D more and smaller than the wild-type form. FRAP microscopy was used to compare nuclear export of both proteins which showed a slightly higher but not significant retention of β-catenin S646D. Altogether, these results show that C-terminal phosphorylation of β-catenin seems to be related with its nucleocytoplasmic transport but not transactivation activity.

DOI: 10.1016/j.gene.2015.07.039

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Cite this paper

@article{Maturana2015TransactivationAA, title={Transactivation activity and nucleocytoplasmic transport of β-catenin are independently regulated by its C-terminal end.}, author={Jose L. Maturana and Ignacio Niechi and Esmeralda Silva and Hern{\'a}n Huerta and Romina Cataldo and Steffen H{\"a}rtel and L Felipe Barros and Mendez Galindo and Johanna Chluba-De Tapia}, journal={Gene}, year={2015}, volume={573 1}, pages={115-22} }