Ataxin-3 suppresses polyglutamine neurodegeneration in Drosophila by a ubiquitin-associated mechanism
Ataxin-3 suppresses polyglutamine neurodegeneration in Drosophila by a ubiquitin-associated mechanism
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DOI：
10.1016/j.molcel.2005.02.030
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发表时间：
2005-04-01
期刊：
影响因子：
16
通讯作者：
Bonini, NM
中科院分区：
文献类型：
--
作者：
Warrick, JM;Morabito, LM;Bonini, NM
多聚谷氨酰胺诱导的神经变性的两个中心问题是疾病蛋白的正常功能的影响和蛋白质质量控制途径的调节。通过使用果蝇，我们现在直接连接到多聚谷氨酰胺疾病脊髓小脑共济失调3型（SCA 3）中的泛素途径的宿主蛋白质功能和疾病发病机制。正常人共济失调蛋白-3-一种具有泛素蛋白酶活性的多聚泛素结合蛋白-是体内多聚谷氨酰胺神经变性的显著抑制剂。这种抑制活性需要蛋白质的泛素相关活性，并依赖于蛋白酶体功能。我们的研究结果强调了SCA 3疾病中宿主蛋白功能的至关重要性，以及共济失调蛋白-3活性对多聚谷氨酰胺疾病的潜在治疗作用。
Two central issues in polyglutamine-induced neuro-degeneration are the influence of the normal function of the disease protein and modulation by protein quality control pathways. By using Drosophila, we now directly link host protein function and disease pathogenesis to ubiquitin pathways in the polyglutamine disease spinocerebellar ataxia type 3 (SCA3). Normal human ataxin-3-a polyubiquitin binding protein with ubiquitin protease activity-is a striking suppressor of polyglutamine neurodegeneration in vivo. This suppressor activity requires ubiquitin-associated activities of the protein and is dependent upon proteasome function. Our results highlight the critical importance of host protein function in SCA3 disease and a potential therapeutic role of ataxin-3 activity for polyglutamine disorders.