Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Neurobiol Dis. 2010 May;38(2):210-8. doi: 10.1016/j.nbd.2010.01.007. Epub 2010 Jan 18.
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.
TRIM 家族蛋白参与广泛的生物学过程，其改变导致遗传疾病、病毒感染和癌症中发现的许多不同的病理状况。然而，TRIM 家族蛋白之一 TRIM9 的时空表达和功能仍然不清楚。我们的研究结果表明，TRIM9 蛋白主要在大脑皮层表达，作为一种 E3 泛素连接酶与 E2 泛素缀合酶 UbcH5b 合作。免疫组织化学检查显示，TRIM9 位于正常小鼠和人脑的神经元中，帕金森病和路易体痴呆症受累脑区的 TRIM9 免疫反应性严重降低。免疫印迹分析支持这种 TRIM9 蛋白水平受到抑制。有趣的是，皮质和脑干型路易体对 TRIM9 呈免疫阳性。这些结果表明，TRIM9 通过其连接酶活性在调节神经元功能中发挥重要作用，并参与路易体疾病的病理过程。
