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

Autor: Maturana JL; Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Niechi I; Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Silva E; Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Huerta H; Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Cataldo R; Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Härtel S; Laboratory for Scientific Image Analysis (SCIAN-Lab), ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Barros LF; Centro de Estudios Cientificos, Valdivia, Chile., Galindo M; Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., Tapia JC; Program of Cellular and Molecular Biology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile. Electronic address: jtapia@med.uchile.cl.
Jazyk: angličtina
Zdroj: Gene [Gene] 2015 Nov 15; Vol. 573 (1), pp. 115-22. Date of Electronic Publication: 2015 Jul 15.
DOI: 10.1016/j.gene.2015.07.039
Abstrakt: 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.
(Copyright © 2015 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE