May 21, 2008

Feedback regulation between zipcode binding protein 1 and beta-catenin mRNAs in breast cancer cells

Molecular and Cellular Biology
Wei GuRobert H Singer

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 beta-catenin, a protein that functions in both cell adhesion and transcription, specifically binds to the ZBP1 promoter via a conserved beta-catenin/TCF4 response element and activates its gene expression. ZBP1 activation is also closely correlated with nuclear translocation of beta-catenin in human breast tumors. We further demonstrate feedback regulation by finding that ZBP1 physically associates with beta-catenin mRNA in vivo and increases its stability. These experiments suggest that in breast cancer cells, the expression of ZBP1 and the expression of beta-catenin are coordinately regulated. beta-Catenin mediates the transcription of the ZBP1 gene, while ZBP1 promotes the stability of beta-catenin mRNA.

  • References42
  • Citations24

References

Mentioned in this Paper

Trans-Activation, Genetic
Neoplasms
Promoter
ZBP1 gene
Embryonic Development
Gene Expression
Staphylococcal Protein A
Binding Protein
TCF4 gene
Nuclear Translocation

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.