线性全方位基因特异性双基因酶皮调节血管生成
Elena Rivkin1, Stephanie M Almeida, Derek F Ceccarelli
1Samuel Lunenfeld Research Institute, Mt Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.
Nature
|May 28, 2013
概括
基因中的两个突变通过影响线性无化,影响Wnt信号传递和胚胎发育来破坏血管形成 (血管生成).
科学领域:
- 分子生物学分子生物学
- 发育生物学 发展生物学
- 生物化学 生物化学
背景情况:
- 血管生成,即新血管的形成,是一个复杂的过程,由像Wnt.这样的信号通路调节.
- 皮 (Fam105b) 基因,特定于 (uro) chordates,涉及到胚胎发育.
研究的目的:
- 为了研究基因在胚胎血管生成中的作用.
- 阐明基突变影响血管生成和Wnt信号传递的分子机制.
主要方法:
- 在具有明显的gumby突变的小鼠中分析胚胎血管新生表型.
- 生物化学测试以确定Gumby的二维基因酶活性和基质特异性.
- 用线性duibiquitin复合的gumby的晶体结构的确定.
- 调查甘与DVL2和HOIP (RNF31) 的相互作用及其对NF-κB信号传递的影响.
主要成果:
- 在小鼠中发现的两种gumby突变导致胚胎血管性缺陷.
- 甘比作为二维基因酶起作用,可以切割线性泛基因链接,与DVL2和HOIP相互作用.
- 突变损害了gumby的基质结合和催化活性,与表型严重程度相关.
- 甘可以负面调节线性无化和NF-κB依赖转录.
结论:
- 甘通过其对线性无处不在的调节,在胚胎血管生成中起着至关重要的作用.
- 这些发现强调了线性 (de) ubiquitination在血管生成,面和神经发育以及Wnt信号调制中的重要性.
- 这项研究提供了机理性的洞察力,了解菌突变如何破坏这些发育过程.
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