Qin Li-Xia, Tan Jie-Qiong, Zhang Hai-Nan, Rizwana Kousar, Lu Jia-Hong, Tang Jian-Guang, Jiang Bo, Shen Xiang-Min, Guo Ji-Feng, Tang Bei-Sha, Tan Li-Ming, Wang Chun-Yu
Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.
The State Key Laboratory of Medical Genetics and School of Life Science, Central South University, Changsha, Hunan, China.
Oxid Med Cell Longev. 2017;2017:5094934. doi: 10.1155/2017/5094934. Epub 2017 Mar 2.
Loss-of-function mutations in gene encoding DJ-1 contribute to the pathogenesis of autosomal recessive early-onset familial forms of Parkinson's disease (PD). DJ-1 is a multifunctional protein and plays a protective role against oxidative stress-induced mitochondrial damage and cell death, but the exact mechanism underlying this is not yet clearly understood. Here, using coimmunoprecipitation (Co-IP) and immunofluorescence methods, we prove that Bcl-2-associated athanogene 5 (BAG5), a BAG family member, interacts with DJ-1 in mammalian cells. Moreover, we show that BAG5 could decrease stability of DJ-1 and weaken its role in mitochondrial protection probably by influencing dimerization in stress condition. Our study reveals the relationship of BAG5 and DJ-1 suggesting a potential role for BAG5 in the pathogenesis of PD through its functional interactions with DJ-1.
编码DJ-1的基因功能缺失突变会导致常染色体隐性早发性家族性帕金森病（PD）的发病。DJ-1是一种多功能蛋白，对氧化应激诱导的线粒体损伤和细胞死亡具有保护作用，但其具体机制尚不清楚。在此，我们利用免疫共沉淀（Co-IP）和免疫荧光方法，证明了BAG家族成员Bcl-2相关抗凋亡蛋白5（BAG5）在哺乳动物细胞中与DJ-1相互作用。此外，我们发现BAG5可能通过影响应激条件下的二聚化来降低DJ-1的稳定性，并削弱其在线粒体保护中的作用。我们的研究揭示了BAG5与DJ-1之间的关系，表明BAG5通过与DJ-1的功能相互作用在PD发病机制中可能发挥作用。
