Differential in vivo requirements for oligomerization during Groucho-mediated repression
Differential in vivo requirements for oligomerization during Groucho-mediated repression
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DOI：
10.1038/sj.embor.7401122
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发表时间：
2008-01-01
期刊：
影响因子：
7.7
通讯作者：
Ish-Horowicz, David
中科院分区：
文献类型：
--
作者：
Jennings, Barbara H.;Wainwright, S. Mark;Ish-Horowicz, David
Groucho（Gro）/transformin-like enhancer of split family of transcriptional corepressors参与许多在发育和疾病中重要的信号传导途径，包括由Notch、Wnt和Hedgehog介导的信号传导途径。在这里，我们描述了一个遗传筛选果蝇产生了50个新的gro等位基因，包括第一个蛋白质无效等位基因，并有两个保守的Q寡聚化结构域已被提出有一个重要的作用，辅阻遏活性的突变。这些后者的突变，编码的氨基末端蛋白质截短，缺乏部分的Q结构域，废除在体外寡聚化，并使蛋白质在体内不稳定。然而，突变不是无效的：母体突变胚胎具有中间分割表型和相对正常的末端图案，这表明突变蛋白保留了部分辅阻遏物活性。我们的研究结果表明，同源寡聚化的GRO是不是强制性的，其在体内的行动，并通过一个以上的GRO抑制转录的分子机制。
The Groucho (Gro)/transducin-like enhancer of split family of transcriptional corepressors are implicated in many signalling pathways that are important in development and disease, including those mediated by Notch, Wnt and Hedgehog. Here, we describe a genetic screen in Drosophila that yielded 50 new gro alleles, including the first protein-null allele, and has two mutations in the conserved Q oligomerization domain that have been proposed to have an essential role in corepressor activity. One of these latter mutations, encoding an amino-terminal protein truncation that lacks part of the Q domain, abolishes oligomerization in vitro and renders the protein unstable in vivo. Nevertheless, the mutation is not a null: maternal mutant embryos have intermediate segmentation phenotypes and relatively normal terminal patterning suggesting that the mutant protein retains partial corepressor activity. Our results show that homo-oligomerization of Gro is not obligatory for its action in vivo, and that Gro represses transcription through more than one molecular mechanism.