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Research Paper
MUC1 Cytoplasmic Domain Coactivates Wnt Target Gene Transcription and Confers Transformation
Lei Huang, Jian Ren, Dongshu Chen, Yongqing Li, Surender Kharbanda and Donald Kufe
volume 2 | issue 6
nov/dec 2003Pages: 702-706
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The DF3/MUC1 mucin-like transmembrane oncoprotein is overexpressed by most human carcinomas. The MUC1 cytoplasmic domain (CD) binds directly to the Wnt effector, beta-catenin, and colocalizes with beta-catenin in the nucleus; however, the nuclear function of MUC1 is unknown. The present results demonstrate that MUC1 coactivates transcription of beta-catenin-Tcf-binding sites in the pTOPFLASH reporter. Activation of transcription was abrogated by expression of MUC1 with a Y-46->F mutation in the CD that attenuates binding of MUC1 and beta-catenin. We also show that transcription of the Wnt responsive cyclin D1 promoter is activated by MUC1, but not MUC1(Y46F), and that the cyclin D1 gene is upregulated in MUC1-positive cells. In concert with these results, MUC1-induced anchorage-independent growth and tumorigenicity were also abrogated by mutating MUC1 at the Y-46 site. These findings support a model in which the MUC1 functions as a transforming protein by coactivating transcription of Wnt target genes.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.