A functional screen in human cells identifies UBF2 as an RNA polymerase II transcription factor that enhances the beta-catenin signaling pathway.

beta-Catenin signaling plays an important role in the development of many organisms and has a key part in driving the malignant transformation of epithelial cells comprising a variety of cancers. beta-Catenin can activate gene expression through its association with transcription factors of the lymphoid enhancer factor 1 (LEF-1)/T-cell factor (TCF) ...
family. We designed a screen in human cells to identify novel genes that activate a beta-catenin-LEF/TCF-responsive promoter and isolated the high-mobility group box transcription factor, UBF2. UBF1 and UBF2 are splice variants of a common precursor RNA. Although UBF1 has been shown to activate RNA polymerase I-regulated genes, the function of UBF2 has remained obscure. Here, we show for the first time that both UBF1 and UBF2 activate RNA polymerase II-regulated promoters. UBF2 associates with LEF-1, as shown by coimmunoprecipitation experiments, and potentiates transcriptional activation stimulated by LEF-1/beta-catenin from a synthetic promoter with multimerized LEF/TCF binding sites and a natural cyclin D1 promoter with consensus LEF/TCF binding sites. Downregulation of endogenous UBF expression using an RNA interference approach reduces transcriptional activation of a beta-catenin-LEF/TCF-responsive promoter by means of overexpressed beta-catenin, further implicating UBF as a transcriptional enhancer of the beta-catenin pathway.
Mesh Terms:
Amino Acid Sequence, Cell Line, Cell Nucleus, Cyclin D1, Cytoskeletal Proteins, DNA-Binding Proteins, Gene Expression Profiling, Gene Expression Regulation, Genes, Reporter, High Mobility Group Proteins, Humans, Lymphoid Enhancer-Binding Factor 1, Molecular Sequence Data, Pol1 Transcription Initiation Complex Proteins, Promoter Regions, Genetic, RNA Polymerase II, Recombinant Fusion Proteins, Sequence Alignment, Signal Transduction, Trans-Activators, Transcription Factors, beta Catenin
Mol. Cell. Biol.
Date: Jun. 01, 2003
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