Carcinogenesis Advance Access published online on April 13, 2007
Carcinogenesis, doi:10.1093/carcin/bgm092
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The CBF1-independent Notch1 signal pathway activates human c-myc expression partially via transcription factor YY1
1 Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
2 Graduate Institute of Cell and Molecular Biology, Taipei Medical University, Taipei 110, Taiwan
3 Graduate Institute of Nutrition and Health Sciences, Taipei Medical University, Taipei 110, Taiwan
4 Department of Life Science, National Chung Cheng University, Chia-Yi 621, Taiwan
5 Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan
* Correspondence: Tien-Shun Yeh, Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, 155, Sec. 2, Li-Nong St., Taipei 112, Taiwan. Tel.: 886-2-2826-7070; Fax: 886-2-2821-2884; E-mail: tsyeh{at}ym.edu.tw
Transcription factor Ying Yang 1 (YY1) indirectly regulates the C promoter-binding factor 1 (CBF1)-dependent Notch1 signaling via direct interaction with the Notch1 receptor intracellular domain on CBF1-response elements. To evaluate the possibility that the Notch1 receptor intracellular domain might modulate the gene expression of YY1 target genes through associating with YY1 on the YY1-response elements, we herein investigated the effect of Notch1 signaling on the expression of YY1 target genes. We found that the Notch1 receptor intracellular domain bound to the double-stranded oligonucleotides of YY1-response element to activate luciferase activity of the reporter gene with YY1-response elements through a CBF1-independent manner. Furthermore, the Notch1 receptor intracellular domain also bound to the promoter of human c-myc oncogene, a YY1 target gene, to elevate c-myc expression via a CBF1-independent pathway. The activation of reporter genes with YY1-response elements or human c-myc promoter by Notch1 receptor intracellular domain depended on the formation of Notch1 receptor intracellular domain-YY1-associated complex. To delineate the role of the Notch signal pathway in tumorigenesis, K562 cell lines expressing the Notch1 receptor intracellular domain were established. Compared with control cells, the proliferation and the tumor growth of Notch1 receptor intracellular domain-expressing K562 cells were suppressed. Taken together, these results suggest that the Notch1 receptor intracellular domain enhances the human c-myc promoter activity which is partially modulated by YY1 through a CBF1-independent pathway. However, the enhancement of c-myc expression by Notch1 receptor intracellular domain is insufficient to promote the tumor growth of K562 cells.
Received December 15, 2006; revised April 4, 2007; accepted April 4, 2007.
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  K.-W. Hsu, R.-H. Hsieh, Y.-H. W. Lee, C.-H. Chao, K.-J. Wu, M.-J. Tseng, and T.-S. Yeh The Activated Notch1 Receptor Cooperates with {alpha}-Enolase and MBP-1 in Modulating c-myc Activity Mol. Cell. Biol., August 1, 2008; 28(15): 4829 - 4842. [Abstract] [Full Text] [PDF]
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