Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-catenin

Curr Biol. 1998 Feb 12;8(4):181-90. doi: 10.1016/s0960-9822(98)70082-x.


Background: Control of the nuclear localization of specific proteins is an important mechanism for regulating many signal transduction pathways. Upon activation of the Wnt signaling pathway, beta-catenin localizes into the nucleus and interacts with TCF/LEF-1 (T-cell factor/lymphocyte enhancer factor-1) transcription factors, triggering activation of downstream genes. The role of regulated nuclear localization in beta-catenin signaling is still unclear. Beta-catenin has no nuclear localization sequence (NLS). Although it has been reported that beta-catenin can piggyback into the nucleus by binding to TCF/LEF-1, there is evidence that its import is independent of TCF/LEF-1 in vivo. Therefore, the mechanism for beta-catenin nuclear localization remains to be established.

Results: We have analyzed beta-catenin nuclear import in an in vitro assay using permeabilized cells. Beta-catenin docks specifically onto the nuclear envelope in the absence of other cytosolic factors. Docking is not inhibited by an NLS peptide and does not require importins/karyopherins, the receptors for classical NLS substrates. Rather, docking is specifically competed by importin-beta/beta-karyopherin, indicating that beta-catenin and importin-beta/beta-karyopherin both interact with common nuclear pore components. Nuclear translocation of beta-catenin is energy dependent and is inhibited by nonhydrolyzable GTP analogs and by a dominant-negative mutant form of the Ran GTPase. Cytosol preparations contain inhibitory activities for beta-catenin import that are distinct from the competition by importin-beta/beta-karyopherin and may be involved in the physiological regulation of the pathway.

Conclusions: Beta-catenin is imported into the nucleus by binding directly to the nuclear pore machinery, similar to importin-beta/beta-karyopherin or other importin-beta-like import factors, such as transportin. These findings provide an explanation for how beta-catenin localizes to the nucleus without an NLS and independently of its interaction with TCF/LEF-1. This is a new and unusual mechanism for the nuclear import of a signal transduction protein. The lack of beta-catenin import activity in the presence of normal cytosol suggests that its import may be regulated by upstream events in the Wnt signaling pathway.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • Biological Transport
  • Cell Nucleus / metabolism*
  • Cytoskeletal Proteins / metabolism*
  • Cytosol / metabolism
  • Karyopherins
  • Nuclear Localization Signals*
  • Nuclear Proteins / metabolism*
  • Recombinant Proteins / metabolism
  • Trans-Activators*
  • Xenopus
  • Xenopus Proteins
  • alpha Karyopherins
  • beta Catenin


  • CTNNB1 protein, Xenopus
  • Cytoskeletal Proteins
  • Karyopherins
  • Nuclear Localization Signals
  • Nuclear Proteins
  • Recombinant Proteins
  • Trans-Activators
  • Xenopus Proteins
  • alpha Karyopherins
  • beta Catenin