Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of β-catenin

摘要

Wnt signaling regulates many aspects of development by increasing the signaling activity of β-catenin. Axin is a negative regulator of the Wnt signaling pathway, and it is responsible for the formation of the β-catenin degradation complex. Genetic studies with Drosophila suggest that Axin promotes cytoplasmic localization of β-catenin independent of Axin's known role of enhancing degradation of β-catenin. Here, we show that Axin is a nuclear-cytoplasmic shuttling protein. Nuclear export of Axin depends on the chromosome maintenance region 1 nuclear receptor; treatment with the chromosome maintenance region 1 inhibitor leptomycin B induces nuclear accumulation of ectopically expressed or endogenous Axin. Functional nuclear localization and nuclear export signals have been mapped within Axin. Significantly, overexpres-sion of an Axin fragment shifts coexpressed stabilized β-catenin to the cytoplasm, and this effect requires shuttling of Axin between the cytoplasm and the nucleus. Our results suggest that Axin functions as a molecular chaperone for β-catenin and that nuclear-cytoplasmic shuttling of Axin regulates the nuclear-cytoplasmic distribution of β-catenin.