DKK1, a negative regulator of Wnt signaling, is a target of the β-catenin/TCF pathway

被引:459
作者
Niida, A
Hiroko, T
Kasai, M
Furukawa, Y
Nakamura, Y
Suzuki, Y
Sugano, S
Akiyama, T
机构
[1] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Mol & Genet Informat, Bunkyo Ku, Tokyo 1130032, Japan
[2] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab,Minato Ku, Tokyo 1088639, Japan
[3] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Lab Genome Database,Minato Ku, Tokyo 1088639, Japan
关键词
DKK1; Wnt; beta-catenin; TCF; TCF-binding element; negative feedback;
D O I
10.1038/sj.onc.1207892
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Wnt signaling plays an important role in embryonic development and tumorigenesis. These biological effects are exerted by activation of the beta-catenin/TCF transcription complex and consequent regulation of a set of downstream genes. TCF-binding elements have been found in the promoter regions of many TCF target genes and characterized by a highly conserved consensus sequence. Utilizing this consensus sequence, we performed an in silico screening for new TCF target genes. Through computational screening and subsequent experimental analysis, we identified a novel TCF target gene, DKK1, which has been shown to be a potent inhibitor of Wnt signaling. Our finding suggests the existence of a novel feedback loop in Wnt signaling.
引用
收藏
页码:8520 / 8526
页数:7
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