MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cong, F.
Right arrow Articles by Varmus, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cong, F.
Right arrow Articles by Varmus, H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2003, p. 8462-8470, Vol. 23, No. 23
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.23.8462-8470.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Requirement for a Nuclear Function of ß-Catenin in Wnt Signaling

Feng Cong, Liang Schweizer, Mario Chamorro, and Harold Varmus*

Program in Cell Biology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021

Received 13 June 2003/ Returned for modification 14 August 2003/ Accepted 3 September 2003

Wnt signaling stabilizes ß-catenin, which in turn influences the transcription of Wnt-responsive genes in conjunction with T-cell factor (TCF) transcription factors. At present, there are two models for the actions of ß-catenin. The conventional nuclear model suggests that ß-catenin acts in the nucleus to form a heterodimeric transcriptional factor complex with TCF, with TCF providing DNA-specific binding and the C and N termini of ß-catenin stimulating transcription. The alternative cytoplasmic model postulates that ß-catenin exports TCF from the nucleus to relieve its repressive activity or activates it in the cytoplasm. We have generated modified forms of ß-catenin and used RNA interference against endogenous ß-catenin to distinguish between these models in cultured mammalian and Drosophila cells. We show that the VP16 transcriptional activation domain can replace the C terminus of ß-catenin without loss of function and that the function of ß-catenin is compromised by fusion to a transcriptional repressor domain from histone deacetylase, favoring the direct effects of ß-catenin in the nucleus. Furthermore, membrane-tethered ß-catenin requires interaction with the adenomatous polyposis coli protein but not with TCF for its function, whereas untethered ß-catenin requires binding to TCF for its signaling activity. Importantly, by using RNA interference, we show that the signaling activity of membrane-tethered ß-catenin, but not free ß-catenin, requires the presence of endogenous ß-catenin, which is able to accumulate in the nucleus when stabilized by the binding of the ß-catenin degradation machinery to the membrane-tethered form. All of these data support a nuclear model for the normal function of ß-catenin.

* Corresponding author. Mailing address: Memorial Sloan-Kettering Cancer Center, 430 East 67th St., RRL 711, New York, NY 10021. Phone: (212) 639-6193. Fax: (212) 717-3125. E-mail: varmus{at}mskcc.org.

Molecular and Cellular Biology, December 2003, p. 8462-8470, Vol. 23, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.23.8462-8470.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2003 by the American Society for Microbiology. All rights reserved.