提基1是通过Wnt裂解氧化和无活化形成头部所需的
Xinjun Zhang1, Jose Garcia Abreu, Chika Yokota
1The F. M. Kirby Neurobiology Center, Boston Children's Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|June 26, 2012
概括
研究人员发现了Tiki1,一种Wnt特异性蛋白酶,对头部形成至关重要. 蒂基1通过分裂Wnt蛋白来禁用Wnt信号,防止受体结合并控制胚胎发育.
科学领域:
- 发育生物学 发展生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 分泌的Wnt形态原体是胚胎发生,再生和疾病的关键信号分子.
- 对于Wnt蛋白来说,它们的功能需要特定的翻译后修改.
- 在发育过程中Wnt蛋白失活的机制在很大程度上是未知的.
研究的目的:
- 在早期发育过程中识别Wnt信号的新型调节者.
- 调查Wnt蛋白失活的潜在机制.
- 了解Tiki1在Xenopus胚胎发生和前部发育中的作用.
主要方法:
- 在Xenopus胚胎中的功能cDNA查.
- 在背部的斯佩曼-曼戈尔德组织器中分析Tiki1的表达.
- 在体外测试以评估Wnt蛋白质裂变和寡合化.
- 在人类细胞中分析Wnt功能.
主要成果:
- 提基1,一种跨膜蛋白质,被确定为Xenopus的前部发育必不可少.
- 蒂基1作为一种Wnt特异性蛋白酶,将Wnt蛋白的氨基末端残留物分离.
- 这种裂变导致氧化Wnt寡合体,其受体结合能力降低.
- 提基1在胚胎和人类细胞环境中对抗Wnt功能.
结论:
- 提基1通过蛋白质分解调解Wnt的失活,从而导致氧化和寡合化.
- 这种机制控制了胚胎发育过程中头部的形成.
- Wnt氨基终端在逃避这种失活路径方面发挥着作用.
- 蒂基1代表了调节Wnt信号的潜在治疗标.
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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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