PMID:10330189

Citation	Prieve, MG and Waterman, ML (1999) Nuclear localization and formation of beta-catenin-lymphoid enhancer factor 1 complexes are not sufficient for activation of gene expression. Mol. Cell. Biol. 19:4503-15
Abstract	In response to activation of the Wnt signaling pathway, beta-catenin accumulates in the nucleus, where it cooperates with LEF/TCF (for lymphoid enhancer factor and T-cell factor) transcription factors to activate gene expression. The mechanisms by which beta-catenin undergoes this shift in location and participates in activation of gene transcription are unknown. We demonstrate here that beta-catenin can be imported into the nucleus independently of LEF/TCF binding, and it may also be exported from nuclei. We have introduced a small deletion within beta-catenin (Delta19) that disrupts binding to LEF-1, E-cadherin, and APC but not axin. This Delta19 beta-catenin mutant localizes to the nucleus because it may not be efficiently sequestered in the cytoplasm. The nuclear localization of Delta19 definitively demonstrates that the mechanisms by which beta-catenin localizes in the nucleus are completely independent of LEF/TCF factors. beta-Catenin and LEF-1 complexes can activate reporter gene expression in a transformed T-lymphocyte cell line (Jurkat) but not in normal T lymphocytes, even though both factors are nuclear. Thus, localization of both factors to the nucleus is not sufficient for activation of gene expression. Excess beta-catenin can squelch reporter gene activation by LEF-1-beta-catenin complexes but not activation by the transcription factor VP16. Taken together, these data suggest that a third component is necessary for gene activation and that this third component may vary with cell type.
Links	PubMed PMC104408
Keywords	Animals; COS Cells; Cadherins/metabolism; Cell Line; Cell Nucleus/metabolism; Cycloheximide/pharmacology; Cytoplasm/metabolism; Cytoskeletal Proteins/metabolism; Cytoskeletal Proteins/physiology; DNA-Binding Proteins/metabolism; DNA-Binding Proteins/physiology; Dactinomycin/pharmacology; Gene Expression Regulation; Humans; Ionomycin/pharmacology; Jurkat Cells; Lymphocytes/metabolism; Lymphoid Enhancer-Binding Factor 1; Microscopy, Fluorescence; Models, Genetic; Mutagenesis; Plasmids; Precipitin Tests; Protein Synthesis Inhibitors/pharmacology; Recombinant Fusion Proteins; Tetradecanoylphorbol Acetate/pharmacology; Trans-Activators; Transcription Factors/metabolism; Transcription Factors/physiology; Transcriptional Activation; beta Catenin
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:CTNB1		GO:0005886: plasma membrane	ECO:0000314:		C		Fig. 3A and B	complete CACAO 9019
HUMAN:CTNB1		GO:0005737: cytoplasm	ECO:0000314:		C		Fig. 3A and B	complete CACAO 9020

References

See Help:References for how to manage references in GONUTS.