Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-catenin
- PMID: 9501980
- DOI: 10.1016/s0960-9822(98)70082-x
Nuclear localization signal-independent and importin/karyopherin-independent nuclear import of beta-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, 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.
Similar articles
-
Beta-catenin can act as a nuclear import receptor for its partner transcription factor, lymphocyte enhancer factor-1 (lef-1).Exp Cell Res. 2005 Aug 15;308(2):357-63. doi: 10.1016/j.yexcr.2005.05.011. Exp Cell Res. 2005. PMID: 15936755
-
Translocation of beta-catenin into the nucleus independent of interactions with FG-rich nucleoporins.Exp Cell Res. 2003 Nov 1;290(2):447-56. doi: 10.1016/s0014-4827(03)00370-7. Exp Cell Res. 2003. PMID: 14568002
-
Distinct nuclear import and export pathways mediated by members of the karyopherin beta family.J Cell Biochem. 1998 Aug 1;70(2):231-9. J Cell Biochem. 1998. PMID: 9671229 Review.
-
Identification and functional characterization of a novel nuclear localization signal present in the yeast Nab2 poly(A)+ RNA binding protein.Mol Cell Biol. 1998 Mar;18(3):1449-58. doi: 10.1128/MCB.18.3.1449. Mol Cell Biol. 1998. PMID: 9488461 Free PMC article.
-
Molecular mechanisms of nuclear protein transport.Crit Rev Eukaryot Gene Expr. 1997;7(1-2):61-72. doi: 10.1615/critreveukargeneexpr.v7.i1-2.40. Crit Rev Eukaryot Gene Expr. 1997. PMID: 9034715 Review.
Cited by
-
Integrative Epigenetic and Molecular Analysis Reveals a Novel Promoter for a New Isoform of the Transcription Factor TEAD4.Int J Mol Sci. 2024 Feb 13;25(4):2223. doi: 10.3390/ijms25042223. Int J Mol Sci. 2024. PMID: 38396900 Free PMC article.
-
APC mutations disrupt β-catenin destruction complex condensates organized by Axin phase separation.Cell Mol Life Sci. 2024 Jan 27;81(1):57. doi: 10.1007/s00018-023-05068-0. Cell Mol Life Sci. 2024. PMID: 38279052 Free PMC article.
-
Phosphorylated PTTG1 switches its subcellular distribution and promotes β-catenin stabilization and subsequent transcription activity.Oncogene. 2023 Aug;42(32):2439-2455. doi: 10.1038/s41388-023-02767-7. Epub 2023 Jul 3. Oncogene. 2023. PMID: 37400529
-
Wnt Signaling Inhibitors and Their Promising Role in Tumor Treatment.Int J Mol Sci. 2023 Apr 4;24(7):6733. doi: 10.3390/ijms24076733. Int J Mol Sci. 2023. PMID: 37047705 Free PMC article. Review.
-
Regulatory role of miRNAs in Wnt signaling pathway linked with cardiovascular diseases.Curr Res Pharmacol Drug Discov. 2022 Oct 1;3:100133. doi: 10.1016/j.crphar.2022.100133. eCollection 2022. Curr Res Pharmacol Drug Discov. 2022. PMID: 36568258 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous