Feedback regulation between zipcode binding protein 1 and beta-catenin mRNAs in breast cancer cells.
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.
Gu
Wei
W
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA. wgu@aecom.yu.edu
Wells
Amber L
AL
Pan
Feng
F
Singer
Robert H
RH
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D051820:TCF Transcription Factors / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C406144:IGF2BP1 protein, human; C498634:Igf2bp1 protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C553059:Tcf7l2 protein, rat; D058118:Transcription Factor 7-Like 2 Protein; D051176:beta Catenin