Huntington and DRPLA proteins selectively interact with the enzyme GAPDH
Huntington and DRPLA proteins selectively interact with the enzyme GAPDH
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DOI：
10.1038/nm0396-347
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发表时间：
1996-03-01
期刊：
影响因子：
82.9
通讯作者：
Strittmatter, WJ
中科院分区：
文献类型：
--
作者：
Burke, JR;Enghild, JJ;Strittmatter, WJ
至少五种成人发病的神经退行性疾病，包括亨廷顿病（HD）和齿状核红核-苍白球路易氏体萎缩（DRPLA）是由编码区内含有显著增加的CAG重复的基因产生的（1-4）。重复序列的大小范围在所有疾病中是相似的;未受影响的个体具有少于30个CAG重复序列，而受影响的患者通常具有超过40个重复序列。遗传性CAG重复序列的大小与疾病的严重程度和发病年龄相关（1，5 -7）。CAG三联体重复序列在表达的蛋白质中产生多聚谷氨酰胺结构域（3，8 -10）。所有这些疾病都以显性方式遗传，并且已经提出了基因携带者的病理性功能获得。我们试图确定大脑中的蛋白质，选择性地与多聚谷氨酰胺结构域蛋白质相互作用，假设多聚谷氨酰胺结构域可能决定蛋白质-蛋白质相互作用。
At least five adult-onset neurodegenerative diseases, including Huntington disease (HD), and dentatorubral-pallidoluysian atrophy (DRPLA) are produced by genes containing a variably increased CAG repeat within the coding region(1-4). The size range of the repeats is similar in all diseases; unaffected individuals have fewer than 30 CAG repeats, whereas affected patients usually have more than 40 repeats. The size of the inherited CAG repeat correlates with the severity and age of disease onset(1,5-7). The CAG triplet repeat produces a polyglutamine domain in the expressed proteins(3,8-10). All of these diseases are inherited in a dominant fashion, and a pathologic gain of function in gene carriers has been proposed. We sought to identify proteins in the brain that selectively interact with polyglutamine domain proteins, hypothesizing that the polyglutamine domain may determine protein-protein interactions.