A HUNTINGTIN-ASSOCIATED PROTEIN ENRICHED IN BRAIN WITH IMPLICATIONS FOR PATHOLOGY
A HUNTINGTIN-ASSOCIATED PROTEIN ENRICHED IN BRAIN WITH IMPLICATIONS FOR PATHOLOGY
复制标题
DOI：
10.1038/378398a0
复制
发表时间：
1995-11-23
期刊：
影响因子：
64.8
通讯作者：
ROSS, CA
中科院分区：
文献类型：
--
作者：
LI, XJ;LI, SH;ROSS, CA
亨廷顿病(HD)是一种常染色体显性遗传性神经退行性疾病，由IT15或亨廷顿蛋白基因(1)中扩增的多谷氨酰胺重复序列引起。尽管该基因广泛表达(2-9)，并且是正常发育所必需的(10-12)，但HD的病理仅限于大脑，原因尚不清楚。亨廷顿蛋白基因产物在患者和对照组中的表达水平相似，该疾病的遗传学(13，14)表明，多谷氨酰胺重复序列的扩张可能通过与其他细胞蛋白的相互作用而诱导有毒的功能获得(15-18)。在这里，我们报告了一种与亨廷丁结合的蛋白质(亨廷顿相关蛋白(HAP)-1)的鉴定。这种结合被扩展的聚谷氨酰胺重复序列增强，该重复序列的长度也已知与发病年龄(19-21岁)相关。HAP-1蛋白在大脑中丰富，这可能是HD选择性脑病理的基础。
HUNTINGTON'S disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanding polyglutamine repeat in the IT15 or huntingtin gene(1). Although this gene is widely expressed(2-9) and is required for normal development(10-12), the pathology of HD is restricted to the brain, for reasons that remain poorly understood. The huntingtin gene product is expressed at similar levels in patients and controls, and the genetics of the disorder(13,14) suggest that the expansion of the polyglutamine repeat induces a toxic gain of function, perhaps through interactions with other cellular proteins(15-18). Here we report the identification of a protein (huntingtin-associated protein (HAP)-1) that binds to huntingtin. This binding is enhanced by an expanded polyglutamine repeat, the length of which is also known to correlate with the age of disease onset(19-21). The HAP-1 protein is enriched in the brain, suggesting a possible basis for the selective brain pathology of HD.