Chuang Jen-Zen, Zhou Hui, Zhu Meicai, Li Shi-Hua, Li Xiao-Jiang, Sung Ching-Hwa
Department of Ophthalmology, Weill Medical College of Cornell University, New York, New York 10012, USA.
J Biol Chem. 2002 May 31;277(22):19831-8. doi: 10.1074/jbc.M109613200. Epub 2002 Mar 14.
Molecular chaperones are involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. DnaK- and DnaJ-like proteins are the two major classes of molecular chaperones in mammals. Recent studies have shown that DnaJ-like family proteins can inhibit polyglutamine aggregation, a hallmark of many neurodegenerative diseases, including Huntington's disease (HD). Although most DnaJ-like proteins studied are ubiquitously expressed, some have restricted expression, so it is possible that some specific chaperones may affect polyglutamine aggregation in specific neurons. In this report, we describe the isolation of a DnaJ-like protein MRJ and the characterization of its chaperone activity. Tissue distribution studies showed that MRJ is highly enriched in the central nervous system. In an in vitro cell model of HD, overexpressed MRJ effectively suppressed polyglutamine-dependent protein aggregation, caspase activity, and cellular toxicity. Collectively, these results suggest that MRJ has a relevant functional role in neurons.
分子伴侣参与广泛的细胞活动，如蛋白质折叠和寡聚蛋白复合物组装。DnaK样蛋白和DnaJ样蛋白是哺乳动物中两类主要的分子伴侣。最近的研究表明，DnaJ样家族蛋白可以抑制多聚谷氨酰胺聚集，这是包括亨廷顿舞蹈症（HD）在内的许多神经退行性疾病的一个标志。虽然大多数已研究的DnaJ样蛋白是普遍表达的，但有些蛋白的表达具有局限性，因此一些特定的分子伴侣可能会在特定神经元中影响多聚谷氨酰胺聚集。在本报告中，我们描述了一种DnaJ样蛋白MRJ的分离及其分子伴侣活性的特征。组织分布研究表明，MRJ在中枢神经系统中高度富集。在HD的体外细胞模型中，过表达的MRJ有效抑制了多聚谷氨酰胺依赖性蛋白聚集、半胱天冬酶活性和细胞毒性。总的来说，这些结果表明MRJ在神经元中具有相关的功能作用。
