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

Abstract

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.

SUPPLEMENTAL MATERIAL

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

ACKNOWLEDGMENTS

This study was supported by NIH grants CA83208 and AR41480 to R.H.S.

We thank K. Lapidus for kindly providing the MTLn3-ZBP1 stable cell line and members of the lab for valuable discussions and suggestions.