USP7, a ubiquitin-specific protease, interacts with ataxin-1, the SCA1 gene product
USP7, a ubiquitin-specific protease, interacts with ataxin-1, the SCA1 gene product
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DOI：
10.1006/mcne.2002.1103
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发表时间：
2002-06-01
影响因子：
3.5
通讯作者：
Kang, S
中科院分区：
文献类型：
--
作者：
Hong, S;Kim, SJ;Kang, S
脊髓小脑性共济失调1型（SCA 1）是一种常染色体显性遗传的神经退行性疾病，其特征是共济失调和进行性运动功能减退。已知SCA 1与共济失调蛋白-1（SCA 1基因产物）中延长的多聚谷氨酰胺束相关。利用酵母双杂交系统，我们发现USP 7，一种泛素特异性蛋白酶，与ataxin-1结合。对缺失突变体的进一步实验表明，共济失调蛋白-1的C末端区域对于相互作用至关重要。液体β-半乳糖苷酶测定和免疫共沉淀实验表明，USP 7和共济失调蛋白-1之间的相互作用强度受共济失调蛋白-1中多聚谷氨酰胺段长度的影响;在具有较长多聚谷氨酰胺段的突变型共济失调蛋白-1中观察到较弱的相互作用，并且在SCA 1转基因小鼠的浦肯野细胞中，USP 7未被募集到突变型共济失调蛋白-1聚集体中。我们的研究结果表明，泛素系统的功能改变可能参与脊髓小脑共济失调1型的发病机制。
Spinocerebellar ataxia type 1 (SCA1) is an autosomal-dominant neurodegenerative disorder characterized by ataxia and progressive motor deterioration. SCA1 has been known to associate with elongated polyglutamine tract in ataxin-1, the SCA1 gene product. Using the yeast two-hybrid system, we have found that USP7, a ubiquitin-specific protease, binds to ataxin-1. Further experiments with deletion mutants indicated that the C-terminal region of ataxin-1 was essential for the interaction. Liquid beta-galactosidase assay and coimmunoprecipitation experiments revealed that the strength of the interaction between USP7 and ataxin-1 is influenced by the length of the polyglutamine tract in the ataxin-1; weaker interaction was observed in mutant ataxin-1 with longer polyglutamine tract and USP7 was not recruited to the mutant ataxin-1 aggregates in the Purkinje cells of SCA1 transgenic mice. Our results suggest that altered function of the ubiquitin system can be involved in the pathogenesis of spinocerebellar ataxia type 1.