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Molecular and Cellular Biology, June 1999, p. 4503-4515, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Nuclear Localization and Formation of beta -Catenin-Lymphoid Enhancer Factor 1 Complexes Are Not Sufficient for Activation of Gene Expression

Mary G. Prieve and Marian L. Waterman*

Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, Irvine, California 92697-4025

Received 16 December 1998/Returned for modification 18 January 1999/Accepted 15 March 1999

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 (Delta 19) that disrupts binding to LEF-1, E-cadherin, and APC but not axin. This Delta 19 beta -catenin mutant localizes to the nucleus because it may not be efficiently sequestered in the cytoplasm. The nuclear localization of Delta 19 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.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, College of Medicine, 19182 Jamboree Blvd., University of California, Irvine, Irvine, CA 92697-4025. Phone: (949) 824-2885. Fax: (949) 824-8598. E-mail: mlwaterm{at}uci.edu.

Molecular and Cellular Biology, June 1999, p. 4503-4515, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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