STRUCTURAL AND FUNCTIONAL STUDIES OF DJ-1

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。人类蛋白DJ-1与遗传性帕金森综合征和某些癌症有关，似乎在保护细胞免受氧化应激的破坏作用方面发挥关键作用。氧化应激与多种疾病的分子发病机制有关，并可能在帕金森病的病因学中起关键作用。DJ-1保护细胞的生化机制尚不清楚，但它通过形成半胱氨酸亚磺酸被活性氧（ROS）特异性修饰。DJ-1的这种氧化激活了抑制α-突触核蛋白的细胞毒性聚集的伴侣蛋白功能，改变了DJ-1的蛋白质结合伴侣，并可能增加定位于线粒体的DJ-1库。

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.