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The Soft Agar Colony Formation Assay
Published on: October 27, 2014
端粒酶通过与色素基因的关联来调节Wnt信号
Jae-Il Park1, Andrew S Venteicher, Ji Yeon Hong
1Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.
Nature
|July 3, 2009
概括
端粒酶通过作为基因转录中的辅因子,直接影响Wnt/β-catenin信号传递. 这一发现揭示了端粒酶.
科学领域:
- 分子生物学分子生物学
- 干细胞生物学 干细胞生物学
- 癌症研究 癌症研究
背景情况:
- 干细胞调节涉及遗传通路,在人类瘤发生过程中经常发生改变.
- Wnt/β-catenin信号传递和端粒酶激活都可以诱导静止的表皮干细胞.
- 连接端粒酶与干细胞激活的确切机制尚不清楚.
研究的目的:
- 阐明端粒酶影响干细胞激活和Wnt/β-catenin信号传递的机制.
- 调查端粒酶在调节Wnt/β-catenin转录活性中的直接作用.
主要方法:
- 研究了端粒酶逆转录酶 (TERT) 和BRG1 (SMARCA4),一种染色体重塑剂之间的相互作用.
- 在培养细胞和体内生物中评估了Wnt-依赖的记者基因活性.
- 使用Xenopus laevis胚胎和Tert-/-) 小鼠检查的发育角色.
- 利用染色体免疫沉检测内源性TERT与Wnt目标基因促进体结合.
主要成果:
- 端粒酶逆转录酶 (TERT) 通过作为辅因子直接调节Wnt/β-catenin信号传递.
- TERT与染色体重塑剂BRG1相互作用,增强了Wnt-依赖转录.
- 在Xenopus中,TERT对于前后轴形成至关重要;Tert缺乏导致小鼠的脊椎缺陷.
- 内源性TERT在体内占据了Wnt响应基因的促进体.
结论:
- 端粒酶作为Wnt/β-catenin信号通路的直接转录调节器.
- 这一发现揭示了端粒酶在DNA延伸中超越其正规功能之外的新角色.
- TERT和染色体重塑复合体之间的相互作用为干细胞调节和癌症提供了新的见解.
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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
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