TRIM9, a novel brain-specific E3 ubiquitin ligase, is repressed in the brain of Parkinson's disease and dementia with Lewy bodies.
TRIM9, a novel brain-specific E3 ubiquitin ligase, is repressed in the brain of Parkinson's disease and dementia with Lewy bodies.
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DOI：
10.1016/j.nbd.2010.01.007
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发表时间：
2010-05
影响因子：
6.1
通讯作者：
Wakabayashi K
中科院分区：
文献类型：
--
作者：
Tanji K;Kamitani T;Mori F;Kakita A;Takahashi H;Wakabayashi K
TRIM家族蛋白参与了广泛的生物学过程，它们的改变导致了遗传病、病毒感染和癌症中的许多不同的病理情况。然而，TRIM家族蛋白TRIM9的时空表达和功能尚不清楚。我们的结果表明，TRIM9蛋白主要在大脑皮层表达，并作为E3泛素连接酶与E2泛素结合酶UbcH5b协同工作。免疫组织化学检测显示，TRIM9定位于正常小鼠和人脑中的神经元，而在帕金森病和路易体痴呆的受累脑区，TRIM9的免疫反应性严重降低。免疫印迹分析支持这种受抑制的TRIM9蛋白水平。有趣的是，皮质和脑干型路易小体对TRIM9呈免疫阳性。这些结果提示，TRIM9在神经元功能调节中起重要作用，并通过其连接酶活性参与了路易体病的病理过程。
TRIM family proteins are involved in a broad range of biological processes, and their alteration results in many diverse pathological conditions found in genetic diseases, viral infections, and cancers. However, the spatial and temporal expression and function of TRIM9, one of TRIM family proteins, remain obscure. Our results here showed that TRIM9 protein is mainly expressed in the cerebral cortex, and functions as an E3 ubiquitin ligase collaborating with an E2 ubiquitin conjugating enzyme UbcH5b. Immunohistochemical examination revealed that TRIM9 is localized to the neurons in the normal mouse and human brain and that TRIM9 immunoreactivity is severely decreased in the affected brain areas in Parkinson’s disease and dementia with Lewy bodies. This repressed level of TRIM9 protein was supported by immunoblotting analysis. Intriguingly, cortical and brainstem-type Lewy bodies were immunopositive for TRIM9. These results suggest that TRIM9 plays an important role in the regulation of neuronal functions and participates in pathological process of Lewy body disease through its ligase activity.
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影响因子：
64.5
作者：
Koegl, M;Hoppe, T;Jentsch, S
通讯作者：
Jentsch, S
影响因子：
9.2
作者：
Freemont, PS
通讯作者：
Freemont, PS
DOI：
10.1016/j.bbrc.2009.02.059
发表时间：
2009-04-10
影响因子：
3.1
作者：
Miyajima, Naoto;Maruyama, Satoru;Hatakeyama, Shigetsugu
通讯作者：
Hatakeyama, Shigetsugu
影响因子：
4.4
作者：
Kong, Hee Jeong;Anderson, D. Eric;Ozato, Keiko
通讯作者：
Ozato, Keiko
影响因子：
3.8
作者：
Eldin, Patrick;Papon, Laura;Mechti, Nadir
通讯作者：
Mechti, Nadir