Site-specific differences in proteasome-dependent degradation of monoubiquitinated α-synuclein.
Site-specific differences in proteasome-dependent degradation of monoubiquitinated α-synuclein.
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DOI：
10.1016/j.chembiol.2013.09.009
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发表时间：
2013-10-24
影响因子：
--
通讯作者：
Pratt MR
中科院分区：
文献类型：
--
作者：
Abeywardana T;Lin YH;Rott R;Engelender S;Pratt MR
主要由α-突触核蛋白组成的有毒聚集体的形成是帕金森病的一个标志。来自人类和动物模型的早发型疾病的证据表明，该疾病的进展与 α-突触核蛋白的表达水平相关，这表明降解过量 α-突触核蛋白的细胞机制是关键。我们和其他人已经证明单泛素化的 α-突触核蛋白可以被 26S 蛋白酶体降解；然而，九个已知的单个单泛素化位点中每一个的贡献尚不清楚。在此，我们使用同质半合成蛋白质并结合体外蛋白酶体周转测定来确定每个修饰位点的后果。数据表明单泛素化的位点特异性效应支持不同水平的 α-突触核蛋白降解。
The formation of toxic aggregates composed largely of the protein α-synuclein are a hallmark of Parkinson’s disease. Evidence from both early-onset forms of the disease in humans and animal models has shown that the progression of the disease is correlated with the expression levels of α-synuclein, suggesting that cellular mechanisms that degrade excess α-synuclein are key. We and others have shown that monoubiquitinated α-synuclein can be degraded by the 26S proteasome; however, the contributions of each of the nine known individual monoubiquitination sites was unknown. Herein we determined the consequences of each of the modification sites using homogenous, semisynthetic proteins in combination with an in vitro proteasome turnover assay. The data suggest that the site-specific effects of monoubiquitination support different levels of α-synuclein degradation.
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影响因子：
168.9
作者：
Chartier-Harlin, MC;Kachergus, J;Destée, A
通讯作者：
Destée, A
影响因子：
56.9
作者：
Singleton, AB;Farrer, M;Gwinn-Hardy, K
通讯作者：
Gwinn-Hardy, K
影响因子：
1.8
作者：
Rabanal, F;DeGrado, WF;Dutton, PL
通讯作者：
Dutton, PL
影响因子：
4.4
作者：
Kim, Yong Man;Jang, Won Hee;Quezado, Martha M.;Oh, Yohan;Chung, Kwang Chul;Junn, Eunsung;Mouradian, M. Maral
通讯作者：
Mouradian, M. Maral
DOI：
10.1126/science.1227157
发表时间：
2012-11-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Luk KC;Kehm V;Carroll J;Zhang B;O'Brien P;Trojanowski JQ;Lee VM
通讯作者：
Lee VM