DKK1, a negative regulator of Wnt signaling, is a target of the β-catenin/TCF pathway
DKK1, a negative regulator of Wnt signaling, is a target of the β-catenin/TCF pathway
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DOI：
10.1038/sj.onc.1207892
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发表时间：
2004-11-04
期刊：
影响因子：
8
通讯作者：
Akiyama, T
中科院分区：
文献类型：
--
作者：
Niida, A;Hiroko, T;Akiyama, T
Wnt信号在胚胎发育和肿瘤发生中起重要作用。这些生物学效应通过激活β-连环蛋白/TCF转录复合物和随后调节一组下游基因来发挥。TCF结合元件存在于许多TCF靶基因的启动子区，具有高度保守的保守序列。利用该共有序列，我们进行了新的TCF靶基因的计算机筛选。通过计算筛选和随后的实验分析，我们确定了一个新的TCF靶基因，DKK 1，这已被证明是一个有效的Wnt信号转导抑制剂。我们的发现表明Wnt信号中存在一个新的反馈回路。
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.