Polyglutamine tracts as modulators of transcriptional activation from yeast to mammals
Polyglutamine tracts as modulators of transcriptional activation from yeast to mammals
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DOI：
10.1515/bc-2011-252
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发表时间：
2012-01-01
影响因子：
3.7
通讯作者：
Schaffner, Walter
中科院分区：
文献类型：
--
作者：
Atanesyan, Lilit;Guenther, Viola;Schaffner, Walter
微卫星重复序列在遗传上是不稳定的，容易膨胀和缩小。它们的一个子集，三联体重复，可以出现在编码区内，并指定氨基酸的同源序列。聚谷氨酰胺(PolyQ)链富含真核调控蛋白，特别是转录因子，我们以前已经证明，它们可以促进哺乳动物细胞的转录激活。在这里，我们还包括了进化分化的生物，即果蝇和面包酵母，从而推广了这一发现。在所有三个系统中，基于Ga14的模型转录因子如果含有多聚Q区，则活性更高，且活性取决于该区的长度。相比之下，多丝氨酸束是不活跃的。多聚Q从内部或C-末端起作用，因此排除了仅仅是结构上的‘连接物’效应。最后，在哺乳动物细胞中进行的双杂交试验表明，多聚Q区可以相互作用，这支持了含有多Q的转录因子可以招募具有多Q区或富含谷氨酰胺的激活结构域的其他因子的概念。调控蛋白中广泛存在的多Q重复序列表明了一种有益的作用；除了对转录活动的贡献外，它们的遗传不稳定性可能有助于物种以一种潜在的可逆方式适应不断变化的环境条件。
Microsatellite repeats are genetically unstable and subject to expansion and shrinkage. A subset of them, triplet repeats, can occur within the coding region and specify homomeric tracts of amino acids. Polyglutamine (polyQ) tracts are enriched in eukaryotic regulatory proteins, notably transcription factors, and we had shown before that they can contribute to transcriptional activation in mammalian cells. Here we generalize this finding by also including evolutionarily divergent organisms, namely, Drosophila and baker's yeast. In all three systems, Ga14-based model transcription factors were more active if they harbored a polyQ tract, and the activity depended on the length of the tract. By contrast, a polyserine tract was inactive. PolyQs acted from either an internal or a C-terminal position, thus ruling out a merely structural 'linker' effect. Finally, a two-hybrid assay in mammalian cells showed that polyQ tracts can interact with each other, supporting the concept that a polyQ-containing transcription factor can recruit other factors with polyQ tracts or glutamine-rich activation domains. The widespread occurrence of polyQ repeats in regulatory proteins suggests a beneficial role; in addition to the contribution to transcriptional activity, their genetic instability might help a species to adapt to changing environmental conditions in a potentially reversible manner.