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Molecular and Cellular Biology, August 2008, p. 4963-4974, Vol. 28, No. 16
0270-7306/08/$08.00+0     doi:10.1128/MCB.00266-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Feedback Regulation between Zipcode Binding Protein 1 and β-Catenin mRNAs in Breast Cancer Cells ^,

Wei Gu,^* Amber L. Wells, Feng Pan, and Robert H. Singer^*

Department of Anatomy and Structural Biology and Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York 10461

Received 15 February 2008/ Returned for modification 14 April 2008/ Accepted 7 May 2008

ZBP1 (zipcode binding protein 1) is an RNA-binding protein involved in many posttranscriptional processes, such as RNA localization, RNA stability, and translational control. ZBP1 is abundantly expressed in embryonic development, but its expression is silenced in most adult tissues. Reactivation of the ZBP1 gene has been reported in various human tumors. In this study, we identified a detailed molecular mechanism of ZBP1 transactivation in breast cancer cells. We show that β-catenin, a protein that functions in both cell adhesion and transcription, specifically binds to the ZBP1 promoter via a conserved β-catenin/TCF4 response element and activates its gene expression. ZBP1 activation is also closely correlated with nuclear translocation of β-catenin in human breast tumors. We further demonstrate feedback regulation by finding that ZBP1 physically associates with β-catenin mRNA in vivo and increases its stability. These experiments suggest that in breast cancer cells, the expression of ZBP1 and the expression of β-catenin are coordinately regulated. β-Catenin mediates the transcription of the ZBP1 gene, while ZBP1 promotes the stability of β-catenin mRNA.

Published ahead of print on 19 May 2008.

Supplemental material for this article may be found at http://mcb.asm.org/.

Present address: Molecular Neurobiology Program, Skirball Institute, New York University Medical Center, New York, NY 10016.