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聚Q蛋白质通过隔离Sis1p伴侣蛋白干扰细胞质蛋白质的核降解
Sae-Hun Park1, Yury Kukushkin, Rajat Gupta
1Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82159 Martinsried, Germany.
Cell
|June 25, 2013
概括
多聚胺 (polyQ) 扩张聚合物隔离Sis1p伴侣,阻断蛋白质清除. 恢复Sis1p水平恢复了蛋白质降解和核进口以进行蛋白质体分解.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 蛋白质质量控制对于预防与蛋白质聚合相关的神经退行性疾病至关重要.
- 无素-蛋白酶体系统 (UPS) 清除错误折叠的蛋白质,但其功能在疾病状态下可能会受到损害.
研究的目的:
- 调查多重胺 (polyQ) 聚合如何破坏UPS错误折叠蛋白质的清除.
- 确定聚Q扩张干扰细胞蛋白质质量控制途径的特定机制.
主要方法:
- 使用了一种表达多Q扩展蛋白的酵母模型和一个错误折叠的蛋白质记者 (CG() -GFP).
- 使用定量蛋白质组分析来识别被隔离的蛋白质.
- 研究了Hsp40伴侣Sis1p及其哺乳动物同类DnaJB1.1.的作用.
主要成果:
- 聚Q扩张抑制了CG() -GFP的UPS介导降解,而不影响无处不在或蛋白质酶活性.
- 聚聚合物隔离了必不可少的Hsp40伴侣Sis1p,这是清除速度限制因素.
- 过度表达Sis1p挽救了CG() -GFP降解.
- Sis1p/DnaJB1调解了错误折叠的蛋白质的核传递,以进行蛋白质体降解,而多Q聚合阻止了这种核导入.
结论:
- 聚Q聚合会通过隔离Sis1p伴侣来损害蛋白质质量控制.
- Sis1p作为传递错误折叠的蛋白质到核中进行UPS降解的关键中间体.
- Sis1p水平对于保持核细胞质蛋白质质量控制途径的效率至关重要.
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