UBQLN2通过蛋白质体调解自独立的蛋白质聚合物清除
Roland Hjerpe1, John S Bett1, Matthew J Keuss2
1Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Davidson Building, Henry Wellcome Lab of Cell Biology, University of Glasgow, G12 8QQ Glasgow, UK; The MRC Protein Phosphorylation and Ubiquitylation Unit, The Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland.
Cell
|August 2, 2016
概括
蛋白质清除对于细胞生存至关重要. 一个新的途径使用UBQLN2和HSP70通过蛋白质组去除蛋白质聚合物,突变导致神经退行.
科学领域:
- 细胞生物学
- 蛋白质降解的分子机制
- 神经科学
背景情况:
- 蛋白质平衡对于细胞的生存至关重要.
- 错误折叠和聚集的蛋白质可能是有毒的.
- 26S蛋白酶降解无处不在的蛋白质,但存在其他途径.
研究的目的:
- 调查蛋白质组穿因子在蛋白质聚合物清除中的作用.
- 阐明UBQLN2对蛋白质稳态的作用机制.
- 了解UBQLN2功能障碍与神经退行之间的联系.
主要方法:
- 研究了UBQLN2,HSP70和26S蛋白质组之间的相互作用.
- 在细胞模型中检查了蛋白质聚合物的清除.
- 评估了UBQLN2突变对陪伴蛋白结合和聚合物清除的影响.
- 在患有UBQLN2突变的小鼠模型中研究认知缺陷.
主要成果:
- UBQLN2与HSP70-HSP110分解酶机制一起作用,通过26S蛋白酶体清除蛋白质聚合物.
- UBQLN2识别了与客户端结合的HSP70并促进了蛋白质的降解.
- 这种核清除途径与自不同.
- 人类UBQLN2突变会损害伴侣结合,总清除,并导致小鼠的认知缺陷.
结论:
- UBQLN2通过一种新的途径在细胞核中清除蛋白质聚合物.
- 这种UBQLN2介导途径的功能障碍导致神经退行性疾病.
- 针对这种途径可能为神经退行提供治疗策略.
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