Parkin is metabolized by the ubiquitin/proteosome system
Parkin is metabolized by the ubiquitin/proteosome system
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DOI：
10.1097/00001756-200008210-00006
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发表时间：
2000-08-21
期刊：
影响因子：
1.7
通讯作者：
Wolozin, B
中科院分区：
文献类型：
--
作者：
Choi, P;Ostrerova-Golts, N;Wolozin, B
Parkin 基因突变会导致常染色体隐性遗传的青少年帕金森症。对散发性帕金森病 (PD) 病例的黑质切片进行的免疫染色显示，帕金在轴突球体和一些路易体中积聚。由于泛素是路易体和轴突球体的主要成分，因此我们研究了 Parkin 是否通过泛素/蛋白体途径代谢。用蛋白体抑制剂 MG132 处理 BE-M17 神经母细胞瘤细胞，产生了一条与双泛素化 Parkin 相对应的条带，通过使用两种不同的抗 Parkin 抗体进行免疫印迹，该条带很明显。这种较高的摩尔。 wt带也与Parkin进行免疫共沉淀。这些数据表明 Parkin 在散发性 PD 的病理生理学中发挥作用，并且 Parkin 是被蛋白酶体复合物降解的泛素化底物。 (C) 2000 Lippincott Williams & Wilkins。
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Immunostaining of substantia nigra sections from sporadic Parkinson's disease (PD) cases shows that Parkin accumulates in axonal spheroids and in some Lewy bodies. Because ubiquitin is a major component of Lewy bodies and axonal spheroids, we investigated whether Parkin is metabolized via the ubiquitin/proteosomal pathway. Treatment of BE-M17 neuroblastoma cells with the proteosomal inhibitor, MG132, produced a band corresponding to di-ubiquitinated Parkin that was apparent by immunoblot using two different anti-Parkin antibodies. This higher mol. wt band also co-immunoprecipitated with Parkin. These data suggest that Parkin plays a role in the pathophysiology of sporadic PD, and that Parkin is a substrate for ubiquitination that is degraded by the proteosomal complex. (C) 2000 Lippincott Williams & Wilkins.