A dynamic exchange of TCF3 and TCF4 transcription factors controls MYC expression in colorectal cancer cells
| Autor: | Meera Shah, Sherri A. Rennoll, Wesley M. Raup-Konsavage, Gregory S. Yochum |
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| Rok vydání: | 2015 |
| Předmět: |
Serum
Transcription Genetic Colorectal cancer Biology Lithium Regulatory Sequences Nucleic Acid Binding Competitive Models Biological Proto-Oncogene Mas Proto-Oncogene Proteins c-myc chemistry.chemical_compound Transcription Factor 4 Transcription (biology) Cell Line Tumor medicine Basic Helix-Loop-Helix Transcription Factors Humans Molecular Biology Transcription factor beta Catenin Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Cell Cycle Wnt signaling pathway Cell Biology TCF4 medicine.disease HCT116 Cells Gene Expression Regulation Neoplastic Repressor Proteins Wnt Proteins medicine.anatomical_structure chemistry TCF3 Gene Knockdown Techniques embryonic structures Cancer research Colorectal Neoplasms Nucleus DNA Developmental Biology Protein Binding Signal Transduction Transcription Factors Reports |
| Zdroj: | Cell cycle (Georgetown, Tex.). 14(3) |
| ISSN: | 1551-4005 |
| Popis: | Deregulated Wnt/β-catenin signaling promotes colorectal cancer (CRC) by activating expression of the c-MYC proto-oncogene (MYC). In the nucleus, the β-catenin transcriptional co-activator binds T-cell factor (TCF) transcription factors, and together TCF/β-catenin complexes activate MYC expression through Wnt responsive DNA regulatory elements (WREs). The MYC 3’ WRE maps 1.4-kb downstream from the MYC transcription stop site and binds TCF4/β-catenin transcription complexes to activate MYC. However, the underlying mechanisms for how this element operates are not fully understood. Here, we report that the TCF family member, TCF3, plays an important role in regulating MYC expression in CRCs. We demonstrate that TCF3 binds the MYC 3′ WRE to repress MYC. When TCF3 is depleted using shRNAs, the MYC 3′ WRE is more available to bind TCF4/β-catenin complexes. Stimulating downstream Wnt/β-catenin signaling by inhibiting GSK3β causes an exchange of TCF3 with TCF4/β-catenin complexes to activate MYC. Finally, this transcription factor switch at the MYC 3′ WRE controls MYC expression as quiescent cells re-enter the cell cycle and progress to S phase. These results indicate that a dynamic interplay of TCF transcription factors governs MYC gene expression in CRCs. |
| Databáze: | OpenAIRE |
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