Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of β-catenin Journal Article
| Authors: | Fagotto, F.; Glück, U.; Gumbiner, B. M. |
| Article Title: | Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of β-catenin |
| Abstract: | 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, β-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 β-catenin signaling is still unclear. β-catenin has no nuclear localization sequence (NLS). Although it has been reported that β-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 β-catenin nuclear localization remains to be established. Results: We have analyzed β-catenin nuclear import in an in vitro assay using permeabilized cells. β-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-β/β karyopherin, indicating that β-catenin and importin-β/β-karyopherin both interact with common nuclear pore components. Nuclear translocation of β-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 β-catenin import that are distinct from the competition by importin-β/β-karyopherin and may be involved in the physiological regulation of the pathway. Conclusions: β-catenin is imported into the nucleus by binding directly to the nuclear pore machinery, similar to importin-β/β-karyopherin or other importin-β like import factors, such as transportin. These findings provide an explanation for how β-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 β-catenin import activity in the presence of normal cytosol suggests that its import may be regulated by upstream events in the Wnt signaling pathway. |
| Keywords: | animal; metabolism; animals; nuclear protein; animalia; nuclear proteins; transactivator protein; recombinant proteins; recombinant protein; trans-activators; cell nucleus; beta catenin; nuclear localization signal; biological transport; cytosol; binding competition; cytoskeleton protein; nuclear localization signals; cytoskeletal proteins; xenopus; karyopherins; binding, competitive; transport at the cellular level; xenopus proteins; article; karyopherin; xenopus protein; beta catenin protein, xenopus; beta-catenin protein, xenopus; karyopherin alpha; alpha karyopherins |
| Journal Title: | Current Biology |
| Volume: | 8 |
| Issue: | 4 |
| ISSN: | 0960-9822 |
| Publisher: | Cell Press |
| Date Published: | 1998-02-12 |
| Start Page: | 181 |
| End Page: | 190 |
| Language: | English |
| PUBMED: | 9501980 |
| PROVIDER: | scopus |
| DOI: | 10.1016/S0960-9822(98)70082-X |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work