Increased expression of p62/SQSTM1 in prion diseases and its association with pathogenic prion protein.
Increased expression of p62/SQSTM1 in prion diseases and its association with pathogenic prion protein.
复制标题
P62/SQSTM1在prion疾病中的表达增加及其与致病性prion蛋白的关联。
DOI：
10.1038/srep04504
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发表时间：
2014-03-28
影响因子：
4.6
通讯作者：
Nishida N
中科院分区：
文献类型：
--
作者：
Homma T;Ishibashi D;Nakagaki T;Satoh K;Sano K;Atarashi R;Nishida N
朊病毒病是以异常折叠的朊病毒蛋白（PrPSc）聚集为特征的神经退行性疾病。在这项研究中，我们专注于清除PrPSc的机制，这仍然不清楚。p62是已知介导异常蛋白聚集体的形成和降解的胞质蛋白。在朊病毒感染的大脑和持续感染的细胞培养物中，p62蛋白的水平增加。在蛋白酶体抑制后，p62与PrPSc共定位，在核周区域形成大的聚集体，下文称为PrPSc-侵袭体。这些聚集体被自噬体标记物LC 3和朊病毒感染细胞中的溶酶体包围。此外，p62的磷酸模拟形式的瞬时表达，它具有增强的泛素结合活性，减少朊病毒感染的细胞中的PrPSc的量，表明p62的激活可以加速PrPSc的清除。因此，我们的研究结果表明，p62可能是朊病毒疾病的治疗控制的目标。
Prion diseases are neurodegenerative disorders characterized by the aggregation of abnormally folded prion protein (PrPSc). In this study, we focused on the mechanism of clearance of PrPSc, which remains unclear. p62 is a cytosolic protein known to mediate both the formation and degradation of aggregates of abnormal proteins. The levels of p62 protein increased in prion-infected brains and persistently infected cell cultures. Upon proteasome inhibition, p62 co-localized with PrPSc, forming a large aggregate in the perinuclear region, hereafter referred to as PrPSc-aggresome. These aggregates were surrounded with autophagosome marker LC3 and lysosomes in prion-infected cells. Moreover, transient expression of the phosphomimic form of p62, which has enhanced ubiquitin-binding activity, reduced the amount of PrPSc in prion-infected cells, indicating that the activation of p62 could accelerate the clearance of PrPSc. Our findings would thus suggest that p62 could be a target for the therapeutic control of prion diseases.
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DOI：
10.1083/jcb.143.7.1883
发表时间：
1998-12-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Johnston JA;Ward CL;Kopito RR
通讯作者：
Kopito RR
影响因子：
4.7
作者：
Babu, JR;Geetha, T;Wooten, MW
通讯作者：
Wooten, MW
影响因子：
4.8
作者：
Fioriti, L;Dossena, S;Chiesa, R
通讯作者：
Chiesa, R
影响因子：
4.8
作者：
Jain, Ashish;Lamark, Trond;Johansen, Terje
通讯作者：
Johansen, Terje
p62/SQSTM1形成自噬降解的蛋白质聚集体，并对亨廷顿蛋白诱导的细胞死亡具有保护作用。
影响因子：
7.8
作者：
Bjorkoy, Geir;Lamark, Trond;Brech, Andreas;Outzen, Heidi;Perander, Maria;Overvatn, Aud;Stenmark, Harald;Johansen, Terje
通讯作者：
Johansen, Terje