STRUCTURAL AND FUNCTIONAL STUDIES OF DJ-1

点击翻译按钮获取中文摘要

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.