STRUCTURAL AND FUNCTIONAL STUDIES OF DJ-1

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。人类蛋白DJ-1与遗传性帕金森氏症和某些癌症有关，似乎在保护细胞免受氧化应激的损害方面发挥了关键作用。氧化应激与几种疾病的分子发病机制有关，并可能在帕金森氏病的病因学中发挥关键作用。DJ-1保护细胞的生化机制尚不清楚，但它可通过形成半胱氨酸亚磺酸而被活性氧簇(ROS)特异性修饰。DJ-1的这种氧化激活了一种伴侣功能，该功能抑制了α-突触核蛋白的细胞毒性聚集，改变了DJ-1的蛋白结合伙伴，并可能增加了定位于线粒体的DJ-1池。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The human protein DJ-1 has been implicated both in hereditary Parkinsonism and in certain cancers and appears to play a critical role in protecting cells from the damaging effects of oxidative stress. Oxidative stress has been linked to the molecular pathogenesis of several diseases, and may play a key role in the etiology of Parkinson's disease. The biochemical mechanism by which DJ-1 protects cells is unknown, however it is specifically modified by reactive oxygen species (ROS) by formation of cysteine sulfinic acid. This oxidation of DJ-1 activates a chaperone function that suppresses the cytotoxic aggregation of alpha-synuclein, alters the protein binding partners for DJ-1, and may increase the pool of DJ-1 that is localized to the mitochondria.