Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of β-catenin Academic Article uri icon

Overview

MeSH Major

  • Cell Nucleus
  • Cytoplasm
  • Cytoskeletal Proteins
  • Repressor Proteins
  • Trans-Activators

abstract

  • Wnt signaling regulates many aspects of development by increasing the signaling activity of beta-catenin. Axin is a negative regulator of the Wnt signaling pathway, and it is responsible for the formation of the beta-catenin degradation complex. Genetic studies with Drosophila suggest that Axin promotes cytoplasmic localization of beta-catenin independent of Axin's known role of enhancing degradation of beta-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, overexpression of an Axin fragment shifts coexpressed stabilized beta-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 beta-catenin and that nuclear-cytoplasmic shuttling of Axin regulates the nuclear-cytoplasmic distribution of beta-catenin.

publication date

  • March 2, 2004

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC365714

Digital Object Identifier (DOI)

  • 10.1073/pnas.0307344101

PubMed ID

  • 14981260

Additional Document Info

start page

  • 2882

end page

  • 7

volume

  • 101

number

  • 9